KR20230084505A - DNA modifying enzymes and active fragments and variants thereof and methods of use - Google Patents

Abstract

Compositions and methods comprising novel deaminase polypeptides for targeted editing of nucleic acids are provided. The composition includes a deaminase polypeptide. Fusion proteins comprising a DNA-binding polypeptide and a deaminase of the invention are also provided. The fusion protein comprises an RNA-guided nuclease fused to a deaminase, optionally in complex with a guide RNA. The composition also includes a nucleic acid molecule encoding the deaminase or fusion protein. Vectors and host cells comprising nucleic acid molecules encoding the deaminase or fusion proteins are also provided.

Description

DNA modifying enzymes and active fragments and variants thereof and methods of use

<Cross Reference to Related Applications>

This application claims priority to U.S. Provisional Application No. 63/077,089, filed September 11, 2020, and U.S. Provisional Application No. 63/146,840, filed February 8, 2021, each of which is incorporated herein by reference in its entirety. included

<Statement Regarding Sequence Listing>

Sequence listings associated with this application are provided in ASCII format in lieu of paper copies and are incorporated herein by reference. An ASCII copy named L103438_1230WO_0108_1_SL.txt is 1,071,246 bytes in size, was created on September 9, 2021, and was submitted electronically via EFS-Web.

<Technical field>

The present invention relates to the fields of molecular biology and gene editing.

Targeted genome editing or modification is rapidly becoming an important tool for basic and applied research. Early methods involved engineering nucleases, such as meganucleases, zinc finger fusion proteins or TALENs, with engineered, programmable, sequence-specific DNA-binding domains specific for each particular target sequence. Requires the generation of chimeric nucleases. RNA-guided nucleases (RGNs), such as the CRISPR-Cas clustered regularly spaced short palindromic repeats (CRISPR)-associated (Cas) proteins of the bacterial system, bind to a guide RNA that specifically hybridizes to a specific target sequence. Complexing the nuclease allows targeting of specific sequences. Generation of target-specific guide RNAs is less expensive and more efficient than generating chimeric nucleases for each target sequence. Using this RNA-guided nuclease, the genome is edited by the introduction of sequence-specific double-strand breaks that are repaired through error-prone non-homologous end-joining (NHEJ), resulting in mutations at specific genomic locations. can be introduced.

Additionally, RGNs are useful for targeted DNA editing approaches. Targeted editing of nucleic acid sequences, for example, targeted cleavage enabling the introduction of specific modifications to genomic DNA, enables a highly nuanced approach to study gene function and gene expression. RGNs can also be used in combination with DNA modifying enzymes, such as deaminase, to create chimeric proteins that use the RNA-guided activity of RGNs for targeted base editing. Targeted editing can be deployed to target genetic diseases in humans or to introduce agronomically beneficial mutations into the genomes of crop plants. The development of genome editing tools provides new approaches to gene editing-based mammalian therapeutics and agricultural biotechnology.

Compositions and methods for modifying a target DNA molecule are provided. The composition is used to modify a target DNA molecule of interest. Provided compositions include deaminase polypeptides. In addition, fusion proteins comprising nucleic acid molecule-binding polypeptides (e.g., DNA-binding polypeptides) and deaminase polypeptides, and fusion proteins comprising RNA-guided nuclease and deaminase polypeptides and ribonucleic acids A ribonucleoprotein complex comprising Provided compositions also include nucleic acid molecules encoding the deaminase polypeptides or fusion proteins, and vectors and host cells comprising the nucleic acid molecules. The methods disclosed herein relate to binding to a target sequence of interest within a target DNA molecule of interest and modifying the target DNA molecule of interest.

The various modifications and other embodiments of the invention presented herein will remind those skilled in the art to which this invention pertains having the benefit of the teachings presented in the above description. It is therefore to be understood that this invention is not limited to the specific embodiments disclosed, and that modifications and other embodiments are intended to be included within the scope of the appended claims. Although specific terms are used herein, they are used in a general and descriptive sense only and not for purposes of limitation.

I. Overview

The present disclosure provides a novel adenine deaminase, and a nucleic acid molecule-binding polypeptide, such as a DNA-binding polypeptide, and a fusion protein comprising the novel deaminase polypeptide. In certain embodiments, a DNA-binding polypeptide is a sequence-specific DNA-binding polypeptide in that it binds to a target sequence with a greater frequency than the DNA-binding polypeptide binds to a randomized background sequence. In some embodiments, the DNA-binding polypeptide is or is derived from a meganuclease, zinc finger fusion protein, or TALEN. In some embodiments, the fusion protein comprises an RNA-guided DNA-binding polypeptide and a deaminase polypeptide. In some embodiments, an RNA-guided DNA-binding polypeptide is an RNA-guided nuclease, such as a Cas9 polypeptide domain, that binds a guide RNA (also referred to as gRNA), which in turn binds to a target nucleic acid sequence via strand hybridization. do.

The deaminase polypeptides disclosed herein are capable of deamination of nucleobases such as adenine. Deamination of nucleobases by deaminase can lead to point mutations at individual residues, referred to herein as "nucleic acid editing" or "base editing". Thus, a fusion protein comprising an RNA-guided nuclease (RGN) polypeptide and a deaminase can be used for targeted editing of nucleic acid sequences.

Such fusion proteins are useful for targeted editing of DNA in vitro, eg, generation of genetically modified cells. These genetically modified cells may be plant cells or animal cells. Such fusion proteins may also be used for the introduction of targeted mutations, eg, correction of genetic defects in mammalian cells ex vivo, eg, in cells obtained from a subject that are subsequently reintroduced into the same or another subject; and introduction of targeted mutations, eg correction of genetic defects in disease-associated genes in mammalian subjects or introduction of inactivating mutations. Such fusion proteins may also be useful for the introduction of targeted mutations in plant cells, for example the introduction of beneficial or agronomically valuable traits or alleles.

The terms "protein", "peptide" and "polypeptide" are used interchangeably herein and refer to a polymer of amino acid residues linked together by peptide (amide) bonds. The term refers to a protein, peptide or polypeptide of any size, structure or function. Typically, a protein, peptide or polypeptide will be at least 3 amino acids in length. A protein, peptide or polypeptide may refer to an individual protein or a collection of proteins. One or more of the amino acids in a protein, peptide, or polypeptide may be, for example, a chemical entity, such as a carbohydrate group, a hydroxyl group, a phosphate group, a farnesyl group, an isofarnesyl group, a fatty acid group, conjugation, functionalization, or other modification. It can be modified by the addition of a linker or the like for A protein, peptide or polypeptide may also be a single molecule or may be a multi-molecular complex. A protein, peptide or polypeptide may only be a fragment of a naturally occurring protein or peptide. A protein, peptide or polypeptide may be naturally occurring, recombinant or synthetic, or any combination thereof.

Any of the proteins provided herein can be produced by any method known in the art. For example, proteins provided herein can be produced through recombinant protein expression and purification, particularly suited to fusion proteins comprising peptide linkers. Methods for recombinant protein expression and purification are well known and are described in Green and Sambrook, Molecular Cloning: A Laboratory Manual (4th ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (2012)) (in its entirety). The contents include those set forth herein, incorporated herein by reference.

II. deaminase

The term “deaminase” refers to an enzyme that catalyzes a deamination reaction. The deaminase of the present invention is a nucleobase deaminase, and the terms "deaminase" and "nucleobase deaminase" are used interchangeably herein. The deaminase can be a naturally-occurring deaminase enzyme or an active fragment or variant thereof. Deaminase can be active against single-stranded nucleic acids such as ssDNA or ssRNA, or against double-stranded nucleic acids such as dsDNA or dsRNA. In some embodiments, the deaminase can only deaminate ssDNA and does not act on dsDNA.

The methods and compositions disclosed herein include adenine deaminase. In some embodiments, the deaminase is an ADAT family deaminase or variant thereof. Deamination of adenine, adenosine or deoxyadenosine yields inosine, which is processed as guanine by polymerases. To date there is no known naturally occurring adenine deaminase that deaminates adenine in DNA. Several methods have been used to evolve and optimize tRNA-acting adenine deaminase (ADAT) proteins to be active against DNA molecules in mammalian cells (Gaudelli et al., 2017; Koblan, L. W. et al., 2018, Nat Biotechnol 36, 843-846; Richter, M. F. et al., 2020, Nat Biotechnol, doi:10.1038/s41587-020-0562-8, each of which is incorporated herein by reference in its entirety). One such method uses a bacterial selection assay in which only cells with the ability to activate antibiotic resistance via A:T>G:C conversion can survive.

The present invention relates to novel adenine deaminase polypeptides produced through evolution and optimization of bacterial deaminase. Novel adenine deaminase is now disclosed and presented herein as SEQ ID NOs: 1-10 and 399-441. The deaminase of the present invention can be used for editing DNA or RNA molecules. In some embodiments, the deaminase of the invention can be used for editing ssDNA or ssRNA molecules. The adenine deaminase described herein is useful as a deaminase alone or as a component of a fusion protein. A fusion protein comprising a DNA-targeting polypeptide and an adenine deaminase polypeptide, referred to herein as an “A-based editor,” “adenine base editor,” or “ABE,” can be used for targeted editing of nucleic acid sequences. .

A “base editing agent” is a fusion protein comprising a DNA-targeting polypeptide such as RGN and a deaminase. Adenine base editrs (ABEs) include DNA-targeting proteins such as RGN and adenine deaminase. ABE functions through the deamination of adenine to inosine on DNA target molecules (Gaudelli, N. M. et al. 2017). Inosine is recognized as guanine by polymerase and allows incorporation of cytosine on the complementary DNA strand opposite inosine. After a round of replication after deamination, a base pair change from A:T to G:C occurs in the genome. In some embodiments, an adenine deaminase or active variant or fragment thereof disclosed herein introduces an A>N mutation into a DNA molecule, where N is C, G, or T. In a further embodiment, they introduce an A>G mutation into the DNA molecule.

In those embodiments in which the deaminase is targeted to a specific region of a nucleic acid molecule through fusion with the DNA-binding polypeptide, the mutation rate of adenine in or adjacent to the target sequence to which the DNA-binding polypeptide binds is determined by polymerase chain reaction (PCR). , restriction fragment length polymorphism (RFLP), or any method known in the art including DNA sequencing.

The novel deaminase disclosed herein, or an active variant or fragment thereof that retains deaminase activity, can be introduced into a cell as part of a deaminase-DNA-binding polypeptide fusion and/or a DNA-binding polypeptide-deaminase. can be co-expressed with the first fusion to increase the efficiency of introducing the desired A>G mutation into the target DNA molecule. The deaminase disclosed herein has an amino acid sequence of any of SEQ ID NOs: 1-10 and 399-441 or a variant or fragment thereof that retains deaminase activity. In some embodiments, the deaminase is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75% relative to the amino acid sequence of any of SEQ ID NOs: 1-10 and 399-441. %, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, have an amino acid sequence that has at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identity. In certain embodiments, the deaminase comprises an amino acid sequence having at least 80% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441. . In some embodiments, the deaminase comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO:407. For example, the deaminase is at least about 80% identical, at least about 90% identical, at least about 95% identical, at least about 96% identical, at least about 97% identical, at least about 98% identical to SEQ ID NO: 407. , an amino acid sequence having at least about 99% identity, at least about 99.5% identity, or at least about 99.9% identity. In some embodiments, the deaminase is at least 80% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, at least 99% identical to SEQ ID NO: 407 , an amino acid sequence having at least 99.5% identity or at least 99.9% identity. In some embodiments, the deaminase comprises the amino acid sequence of SEQ ID NO: 407. In some embodiments, the deaminase comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO:399. For example, the deaminase is at least about 80% identical, at least about 90% identical, at least about 95% identical, at least about 96% identical, at least about 97% identical, at least about 98% identical to SEQ ID NO: 399. , an amino acid sequence having at least about 99% identity, at least about 99.5% identity, or at least about 99.9% identity. In some embodiments, the deaminase is at least 80% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, at least 99% identical to SEQ ID NO: 399 , an amino acid sequence having at least 99.5% identity or at least 99.9% identity. In some embodiments, the deaminase comprises the amino acid sequence of SEQ ID NO: 399. In some embodiments, the deaminase comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO:405. For example, the deaminase is at least about 80% identical, at least about 90% identical, at least about 95% identical, at least about 96% identical, at least about 97% identical, at least about 98% identical to SEQ ID NO: 405 , an amino acid sequence having at least about 99% identity, at least about 99.5% identity or at least about 99.9% identity. In some embodiments, the deaminase is at least 80% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, at least 99% identical to SEQ ID NO: 405 , an amino acid sequence having at least 99.5% identity or at least 99.9% identity. In some embodiments, the deaminase comprises the amino acid sequence of SEQ ID NO: 405.

III. Nucleic Acid Molecule-Binding Polypeptide

Some aspects of the present disclosure provide fusion proteins comprising a nucleic acid molecule-binding polypeptide and a deaminase polypeptide. Although binding to RNA molecules and targeted editing thereof is contemplated by the present invention, in some embodiments, the nucleic acid molecule-binding polypeptide of the fusion protein is a DNA-binding polypeptide. Such fusion proteins are useful for targeted editing of DNA in vitro, ex vivo or in vivo. These novel fusion proteins are active in mammalian cells and are useful for targeted editing of DNA molecules.

As used herein, the term "fusion protein" refers to a hybrid polypeptide comprising protein domains from at least two different proteins. A fusion protein can include more than one different domain, such as a DNA-binding domain and a deaminase. In some embodiments, the fusion protein is in complex with or associated with a nucleic acid, such as RNA.

In some embodiments, a fusion protein disclosed herein comprises a DNA-binding polypeptide. As used herein, the term “DNA-binding polypeptide” refers to any polypeptide capable of binding DNA. In certain embodiments, the DNA-binding polypeptide portion of a fusion protein disclosed herein binds double-stranded DNA. In certain embodiments, a DNA-binding polypeptide binds DNA in a sequence-specific manner. As used herein, the term “sequence-specific” or “sequence-specific manner” refers to selective interactions with specific nucleotide sequences.

Two polynucleotide sequences are considered substantially complementary when the two sequences hybridize to each other under stringent conditions. Likewise, a DNA-binding polypeptide is considered to bind a particular target sequence in a sequence-specific manner if the DNA-binding polypeptide binds to that sequence under stringent conditions. "Stringent conditions" or "stringent hybridization conditions" are conditions in which two polynucleotide sequences (or polypeptides bind to their specific target sequence) are detectably greater than the other sequence (e.g., at least 2-fold over background). ) is a condition intended to be combined with each other. Stringent conditions are sequence-dependent and will be different in different circumstances. Typically, stringent conditions are a salt concentration of less than 1.5 M Na ions, typically about 0.01 to 1.0 M Na ions (or other salts) at pH 7.0 to 8.3, and a short sequence (e.g., 10 to 50 salts) at pH 7.0 to 8.3. nucleotides) and at least 60°C for long sequences (eg, greater than 50 nucleotides). Stringent conditions can also be achieved with the addition of destabilizing agents such as formamide. Exemplary low stringency conditions include hybridization with a buffer solution of 30-35% formamide, 1 M NaCl, 1% SDS (sodium dodecyl sulfate) at 37°C, and 1X-2X SSC (20X) at 50-55°C. SSC = 3.0 M NaCl/0.3 M trisodium citrate). Exemplary moderate stringency conditions include hybridization in 40-45% formamide, 1.0 M NaCl, 1% SDS at 37°C, and a wash in 0.5X-1X SSC at 55-60°C. Exemplary high stringency conditions include hybridization in 50% formamide, 1 M NaCl, 1% SDS at 37°C, and a wash in 0.1X SSC at 60-65°C. Optionally, the wash buffer may include about 0.1% to about 1% SDS. Hybridization duration is generally less than about 24 hours, usually about 4 to about 12 hours. The wash duration will be at least sufficient to reach equilibrium.

Tm is the temperature at which (under defined ionic strength and pH) 50% of the complementary target sequence hybridizes perfectly to the matched sequence. For DNA-DNA hybrids, Tm is determined by Meinkoth and Wahl (1984) Anal. Biochem. 138:267-284]: Tm = 81.5°C + 16.6 (log M) + 0.41 (%GC) - 0.61 (% form) - 500/L; where M is the molarity of monovalent cations, %GC is the percentage of guanosine and cytosine nucleotides in DNA, % form is the percentage of formamide in the hybridization solution, and L is the length of the hybrid in base pairs. Generally, stringent conditions are selected to be about 5° C. lower than the thermal melting point (Tm) for a particular sequence and its complement at a defined ionic strength and pH. However, highly stringent conditions may utilize hybridization and/or washes that are 1, 2, 3, or 4° C. lower than the thermal melting point (Tm); Moderately stringent conditions may utilize hybridization and/or washes that are 6, 7, 8, 9, or 10° C. lower than the thermal melting point (Tm); Low stringency conditions may utilize hybridizations and/or washes 11, 12, 13, 14, 15, or 20° C. lower than the thermal melting point (Tm). Using the equations, the hybridization and wash compositions, and the desired Tm, one skilled in the art will understand that variations in stringency of hybridization and/or wash solutions are essentially described. Extensive guidelines for hybridization of nucleic acids are found in Tijssen (1993) Laboratory Techniques in Biochemistry and Molecular Biology-Hybridization with Nucleic Acid Probes, Part I, Chapter 2 (Elsevier, New York); and Ausubel et al., eds. (1995) Current Protocols in Molecular Biology, Chapter 2 (Greene Publishing and Wiley-Interscience, New York). See Sambrook et al. (1989) Molecular Cloning: A Laboratory Manual (2d ed., Cold Spring Harbor Laboratory Press, Plainview, New York).

In certain embodiments, the sequence-specific DNA-binding polypeptide is an RNA-guided, DNA-binding polypeptide (RGDBP). As used herein, the terms "RNA-guided, DNA-binding polypeptide" and "RGDBP" refer to a polypeptide capable of binding DNA through hybridization of an associated RNA molecule with a target DNA sequence.

In some embodiments, the DNA-binding polypeptide of the fusion protein is a nuclease, such as a sequence-specific nuclease. As used herein, the term “nuclease” refers to an enzyme that catalyzes the cleavage of phosphodiester bonds between nucleotides in a nucleic acid molecule. In some embodiments, the DNA-binding polypeptide is an endonuclease capable of cleaving phosphodiester bonds between nucleotides in a nucleic acid molecule, whereas in certain embodiments, the DNA-binding polypeptide is at either end of a nucleic acid molecule (5 ' or 3') is an exonuclease capable of cleaving nucleotides. In some embodiments, the sequence-specific nuclease is a meganuclease, a zinc finger nuclease, a TAL-effector DNA binding domain-nuclease fusion protein (TALEN), and an RNA-guided nuclease (RGN). ), or a variant thereof having reduced or inhibited nuclease activity.

As used herein, the term “meganuclease” or “homing endonuclease” refers to an endonuclease that binds to a recognition site in double-stranded DNA between 12 and 40 bp in length. A non-limiting example of a meganuclease belongs to the LAGLIDADG family, which includes the conserved amino acid motif LAGLIDADG (SEQ ID NO: 49). The term “meganuclease” may refer to either dimeric or single-stranded meganucleases.

As used herein, the term "zinc finger nuclease" or "ZFN" refers to a chimeric protein comprising a zinc finger DNA-binding domain and a nuclease domain.

As used herein, the term “TAL-effector DNA binding domain-nuclease fusion protein” or “TALEN” refers to a chimeric protein comprising a TAL effector DNA-binding domain and a nuclease domain.

As used herein, the term “RNA-guided nuclease” or “RGN” refers to an RNA-guided, DNA-binding polypeptide that has nuclease activity. RGNs are considered "RNA-guided", which means that the guide RNA forms a complex with the RNA-guided nuclease so that the RNA-guided nuclease binds to the target sequence and, in some embodiments, to the target sequence. -because it directs to introduce stranded or double-stranded breaks. RGNs are CasX, CasY, C2c1, C2c2, C2c3, GeoCas9, aSpCas9, SaCas9, Nme2Cas9, CjCas9, Cas12a (previously known as Cpf1), Cas12b, Cas12g, Cas12h, Cas12i, LbCas12a, AsCas12a, CasMINI, Cas13b, Cas13c, Cas13d, Cas14, Csn2, xCas9, SpCas9-NG, LbCas12a, AsCas12a, Cas9-KKH, circular permutation Cas9, Argonaut (Ago), SmacCas9, or Spy-macCas9, Spy-macCas9 domain, or SEQ ID NO: 41, 60, 366, or an RGN having the amino acid sequence set forth in either 368. In some embodiments, as described below, an RGN provided herein is an RGN nickase.

According to the present invention, an RGN protein mutated to be nuclease-inactive or "loss-of-function", such as dCas9, is an RNA-guided, DNA-binding polypeptide or nuclease-inactive RGN or nuclease-loss-of-function RGN. may be referred to as Additionally, suitable nuclease-inactive Cas9 domains of other known RNA guided nucleases (RGNs) can be determined (eg, US Patent Publication No. 2019/0367949, the entire contents of which are incorporated herein by reference). a nuclease-inactive variant of RGN APG08290.1 disclosed in ).

In some embodiments, the fusion protein comprises an RGN fused to a deaminase described herein. In an embodiment of the fusion protein described above, the deaminase is selected from deaminase comprising an amino acid sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-10 and 399-441. In some embodiments, the deaminase comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO:407. In some embodiments, the deaminase comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO:399. In some embodiments, the deaminase comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO:405. In an embodiment of the fusion protein described above, the RGN is CasX, CasY, C2c1, C2c2, C2c3, GeoCas9, aSpCas9, SaCas9, Nme2Cas9, CjCas9, Cas12a (previously known as Cpf1), Cas12b, Cas12g, Cas12h, Cas12i, LbCas12a , AsCas12a, CasMINI, Cas13b, Cas13c, Cas13d, Cas14, Csn2, xCas9, SpCas9-NG, LbCas12a, AsCas12a, Cas9-KKH, circular permutation Cas9, Argonaut (Ago), SmacCas9, Spy-macCas9 domain, or SEQ ID NO: 41, 60, 366, or 368 are selected from RGNs having the amino acid sequence set forth in any one of them. In a specific embodiment, the fusion protein comprises a Cas9 nickase fused to a deaminase comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO:407. In some embodiments, the fusion protein comprises a Cas9 nickase fused to a deaminase comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO:399. In a specific embodiment, the fusion protein comprises a Cas9 nickase fused to a deaminase comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO:405. The Cas9 nickase can be any Cas9 nickase disclosed in PCT Patent Publication No. WO2020181195, the entire contents of which are incorporated herein by reference.

The term "RGN polypeptide" includes RGN polypeptides that cleave only a single strand of a target nucleotide sequence, and are referred to herein as nickases. These RGNs have a single functional nuclease domain. RGN nickases can be naturally-occurring nickases, or they can spontaneously cleave both strands of a double-stranded nucleic acid molecule that has been mutated within one or more nuclease domains, thereby reducing or eliminating the nuclease activity of these mutated domains, resulting in nicking. It may be an RGN protein that causes In some embodiments, the nickase RGN of the fusion protein has a mutation (e.g., D10A mutations). This D10A mutation mutates the first aspartic acid residue in the split RuvC nuclease domain of RGN. This application discloses several D10A nickase variants or homologous nickase variants of the described RGNs (see Example 4). nAPG07433.1 and nAPG08290.1 (represented by SEQ ID NOs: 42 and 61, respectively) are nickase variants of APG07433.1 and APG08290.1, represented by SEQ ID NOs: 41 and 60, respectively, and described in WO 2019/236566 (the entire text thereof). incorporated herein by reference). nAPG00969 (shown as SEQ ID NO: 52) and nAPG09748 (shown as SEQ ID NO: 54) are nickase variants of APG00969 and APG09748, respectively, which are described in WO 2020/139783, which is incorporated herein by reference in its entirety. there is. nAPG06646 (shown as SEQ ID NO: 53) and nAPG09882 (shown as SEQ ID NO: 55) are nickase variants of APG06646 and APG09882, respectively, which are disclosed in PCT Publication WO 2021/030344, which is incorporated herein by reference in its entirety. are listed. nAPG03850, nAPG07553, nAPG055886, and nAPG01604 are respectively set forth as SEQ ID NOs: 56-59 and described in pending PCT Application No. PCT/US2021/028843, which is incorporated herein by reference in its entirety, APG03850, APG07553, APG055886, and It is a nickase variant of APG01604. Various RGN nickases, variants thereof and sequences thereof are disclosed in PCT Patent Publication No. WO2020181195, the entire contents of which are incorporated herein by reference. One exemplary suitable nuclease-inactive Cas9 is the D10A/H840A Cas9 mutant (see, eg, Qi et al., Cell. 2013; 152(5): 1173-83, the entire contents of which are herein incorporated by reference).

In some embodiments, the nickase RGN of the fusion protein comprises a mutation (e.g., the H840A mutation), wherein the RGN is base-edited, non-targeted strand of the nucleic acid duplex (not including the PAM and unpaired strand). The H840A mutation mutates the first histidine of the HNH nuclease domain. The nickase RGN containing the H840A mutation or an equivalent mutation has an inactivated HNH domain. The nickase RGN with the H840A mutation cleaves the non-targeted strand. Nickases containing the D10A mutation or an equivalent mutation have an inactivated RuvC nuclease domain and cleave the targeted strand. D10A nickase cannot cleave the non-targeted strand of DNA, i.e. the strand for which base editing is required.

Other additional exemplary suitable nuclease inactive Cas9 domains include, but are not limited to, D10A/D839A/H840A, and D10A/D839A/H840A/N863A mutant domains (see, e.g., Mali et al., Nature Biotechnology. 2013;31(9): 833-838, the entire contents of which are incorporated herein by reference). Additional suitable RGN proteins mutated with nickases are based on this disclosure and knowledge in the art (such as, for example, the RGNs disclosed in PCT Publication Nos. WO 2019/236566, WO2020181195, which are incorporated herein by reference in their entirety) will be apparent to those skilled in the art and are within the scope of this disclosure. In a preferred embodiment, RGNs having nickase activity on the target strand nick the target strand, while the complementary non-target strand is modified by the deaminase. Cellular DNA-repair machinery can introduce mutations into DNA by repairing the nicked target strand using the modified non-target strand as a template.

In some embodiments, the RGN nickase-bearing nickase activity is at least 60%, at least 65%, at least 70%, at least relative to SEQ ID NO: 42 or any one of SEQ ID NOs: 52-59, 61, 397, and 398 amino acid sequences that have at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or at least 99.5% identity.

Any method known in the art for introducing mutations into amino acid sequences, such as PCR-mediated mutagenesis and site-directed mutagenesis, can be used to generate nickase or nuclease-defective RGNs. . See, eg, US Publication No. 2014/0068797 and US Patent No. 9,790,490; Each of these is incorporated herein by reference in its entirety. RNA-guided nucleases (RGNs) allow targeted manipulation of single sites within the genome and are useful in the context of gene targeting for therapeutic and research uses. In various organisms, including mammals, RNA-guided nucleases have been used for genome engineering by stimulating non-homologous end joining or homologous recombination. RGNs are part of the clustered regularly spaced short palindromic repeats (CRISPR) RNA-guided nuclease system, the CRISPR-Cas protein, an RNA-guided nuclease directed to a target sequence by a guide RNA (gRNA). , or active variants or fragments thereof.

An RGN polypeptide (and a nucleic acid molecule encoding an RGN polypeptide) comprising the amino acid sequence set forth in SEQ ID NO: 41 or 60 but lacking amino acid residues 590 to 597 of SEQ ID NO: 41 or 60, or an active variant or fragment thereof, Further provided herein. In certain embodiments, the RGN polypeptide comprises an amino acid sequence set forth in SEQ ID NO: 366, 368, 397 or 398 or an active variant or fragment thereof.

Some aspects of the present disclosure provide fusion proteins comprising an RNA-guided DNA-binding polypeptide and a deaminase polypeptide, specifically an adenine deaminase polypeptide. In some embodiments, an RNA-guided DNA-binding polypeptide is an RNA-guided nuclease. In a further embodiment, the RNA-guided nuclease is a naturally-occurring CRISPR-Cas protein or an active variant or fragment thereof. CRISPR-Cas systems are classified as class 1 or class 2 systems. Class 2 systems contain single effector nucleases and include types II, V and VI. Class 1 and 2 systems are subdivided into types (types I, II, III, IV, V, and VI), and some types are subtypes (e.g., type II-A, type II-B, type II-C, It is further subdivided into Type V-A, Type V-B).

In certain embodiments, the CRISPR-Cas protein is a naturally-occurring type II CRISPR-Cas protein or an active variant or fragment thereof. As used herein, the terms "Type II CRISPR-Cas protein", "Type II CRISPR-Cas effector protein", or "Cas9" require a trans-activating RNA (tracrRNA) and, respectively, a single strand of a double-stranded DNA molecule. Refers to a CRISPR-Cas effector protein comprising two nuclease domains responsible for cleaving (ie, RuvC and HNH). In some embodiments, the invention provides a fusion protein comprising a deaminase disclosed herein fused to Streptococcus pyogenes Cas9 (SpCas9) or SpCas9 nickase, the sequences of which are SEQ ID NOs: 555 and 556 and described in U.S. Patent Nos. 10,000,772 and 8,697,359, each incorporated herein by reference in its entirety. In some embodiments, the invention provides a fusion protein comprising a deaminase disclosed herein fused to Streptococcus thermophilus Cas9 (StCas9) or a StCas9 nickase, the sequences of which are SEQ ID NOs: 557 and 558 and disclosed in U.S. Patent No. 10,113,167, which is incorporated herein by reference in its entirety. In some embodiments, the invention provides a fusion protein comprising a deaminase disclosed herein fused to Streptococcus aureus Cas9 (SaCas9) or a SaCas9 nickase, the sequences of which are SEQ ID NOs: 559 and 560, and disclosed in US Pat. No. 9,752,132, which is incorporated herein by reference in its entirety.

In some embodiments, the CRISPR-Cas protein is a naturally-occurring Type V CRISPR-Cas protein or an active variant or fragment thereof. As used herein, the term "Type V CRISPR-Cas protein", "Type V CRISPR-Cas effector protein" or "Cas12" cleave dsDNA and include a single RuvC nuclease domain or a split-RuvC nuclease domain and Refers to CRISPR-Cas effector proteins lacking the HNH domain (Zetsche et al. 2015, Cell doi:10.1016/j.cell.2015.09.038; Shmakov et al. 2017, Nat Rev Microbiol doi:10.1038/nrmicro. 2016.184; Yan et al. 2018, Science doi:10.1126/science.aav7271;Harrington et al. Cas12a is also referred to as Cpf1 and does not require tracrRNA, but it should be noted that other type V CRISPR-Cas proteins, such as Cas12b, require tracrRNA. Most type V effectors can also target ssDNA (single-stranded DNA), often without a PAM requirement (Zetsche et al. 2015; Yan et al. 2018; Harrington et al. 2018). The term “Type V CRISPR-Cas protein” refers to a unique RGN comprising a split RuvC nuclease domain, such as U.S. Provisional Application Nos. Application), and PCT International Application No. PCT/US2020/067138 filed on December 28, 2020, the contents of each of which are incorporated herein by reference in their entirety. In some embodiments, the present invention relates to Francisella novicida Cas12a (FnCas12a), the sequence of which is set forth as SEQ ID NO: 561 and is disclosed in U.S. Patent No. 9,790,490, which is incorporated herein by reference in its entirety; or Fusion proteins comprising the deaminase disclosed herein fused to any of the nuclease-inactivating mutants of FnCas12a disclosed in US Pat. No. 9,790,490 are provided.

In some embodiments, the CRISPR-Cas protein is a naturally occurring Type VI CRISPR-Cas protein or an active variant or fragment thereof. As used herein, the term "Type VI CRISPR-Cas protein", "Type VI CRISPR-Cas effector protein" or "Cas13" refers to a CRISPR-Cas effector comprising two HEPN domains that cleave RNA without requiring tracrRNA. refers to proteins.

The term "guide RNA" refers to a nucleotide sequence that has sufficient complementarity with a target nucleotide sequence to hybridize with the target sequence and directs sequence-specific binding of the target nucleotide sequence to an associated RGN. For CRISPR-Cas RGNs, each guide RNA is one or more RNA molecules (typically 1 or 2) capable of binding to the RGN and guiding the RGN to a specific target nucleotide sequence, wherein the RGN is a nickase or when it has nuclease activity, it also cleave the target nucleotide sequence. Guide RNAs include CRISPR RNAs (crRNAs), and in some embodiments trans-activating CRISPR RNAs (tracrRNAs).

CRISPR RNA includes spacer sequences and CRISPR repeat sequences. A “spacer sequence” is a nucleotide sequence that directly hybridizes with a target nucleotide sequence of interest. The spacer sequence is engineered to be fully or partially complementary to the target sequence of interest. In various embodiments, the spacer sequence comprises from about 8 nucleotides to about 30 nucleotides, or more. For example, the spacer sequence is about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25, about 26, about 27, about 28, about 29, about 30, or more nucleotides in length. In some embodiments, the spacer sequence is 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or more nucleotides in length. In some embodiments, the spacer sequence is about 10 to about 26 nucleotides in length, or about 12 to about 30 nucleotides in length. In some embodiments, the spacer sequence is 10 to 26 nucleotides in length, or 12 to 30 nucleotides in length. In certain embodiments, the spacer sequence is about 30 nucleotides in length. In certain embodiments, the spacer sequence is 30 nucleotides in length. In some embodiments, the degree of complementarity between a spacer sequence and its corresponding target sequence when optimally aligned using a suitable alignment algorithm is 50% to 99% or greater, such as but not limited to about 50%, about 60%, About 70%, about 75%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90 %, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more. In certain embodiments, the degree of complementarity between a spacer sequence and its corresponding target sequence when optimally aligned using a suitable alignment algorithm is 50%, 60%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% , or more. In certain embodiments, the spacer sequence contains no secondary structure, which is mFold (see, eg, Zuker and Stiegler (1981) Nucleic Acids Res. 9:133-148) and RNAfold (eg, It can be predicted using any suitable polynucleotide folding algorithm known in the art including, but not limited to, Gruber et al. (2008) Cell 106(1):23-24).

A CRISPR RNA repeat sequence contains a nucleotide sequence that forms a structure recognized by an RGN molecule by itself or together with a hybridized tracrRNA. In various embodiments, the CRISPR RNA repeat sequence comprises between about 8 nucleotides and about 30 nucleotides, or more. In certain embodiments, the CRISPR RNA repeat sequence comprises 8 nucleotides to 30 nucleotides, or more. For example, a CRISPR repeat sequence can be about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25, about 26, about 27, about 28, about 29, about 30, or more nucleotides in length. In certain embodiments, the CRISPR repeat sequence is 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28 , 29, 30, or more nucleotides in length. In some embodiments, the degree of complementarity between a CRISPR repeat sequence and its corresponding tracrRNA sequence when optimally aligned using a suitable alignment algorithm is between 50% and 99%, or greater, such as but not limited to about 50%, about 60%, about 70%, about 75%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89% , about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more. In certain embodiments, the degree of complementarity between a CRISPR repeat sequence and its corresponding tracrRNA sequence when optimally aligned using a suitable alignment algorithm is 50%, 60%, 70%, 75%, 80%, 81%, 82 %, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more.

In some embodiments, the guide RNA further comprises a tracrRNA molecule. A trans-activating CRISPR RNA or tracrRNA molecule comprises a nucleotide sequence comprising a region with sufficient complementarity to hybridize to a CRISPR repeat sequence of a crRNA, referred to herein as an anti-repeat region. In some embodiments, the tracrRNA molecule further comprises a region having secondary structure (eg, a stem-loop) or forms a secondary structure upon hybridization with its corresponding crRNA. In certain embodiments, the region of the tracrRNA that is fully or partially complementary to the CRISPR repeat sequence is at the 5' end of the molecule, and the 3' end of the tracrRNA comprises a secondary structure. These regions of secondary structure usually contain several hairpin structures found adjacent to anti-repeat sequences, such as nexus hairpins. Often at the 3' end of the tracrRNA there is a GC-rich Rho-independent transcription terminator hairpin, which can vary in structure and number, but is often followed by a terminal hairpin containing a string of U's at the 3' end. See, eg, Briner et al. (2014) Molecular Cell 56:333-339, Briner and Barrangou (2016) Cold Spring Harb Protoc; doi: 10.1101/pdb.top090902] and US Publication No. 2017/0275648, each of which is incorporated herein by reference in its entirety.

In various embodiments, the anti-repeat region of a tracrRNA that is fully or partially complementary to a CRISPR repeat sequence comprises from about 6 nucleotides to about 30 nucleotides or more. For example, the base pairing region between the tracrRNA anti-repeat sequence and the CRISPR repeat sequence is about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, About 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25, about 26, about 27, about 28, about 29, about 30, or more It can be nucleotides in length. In certain embodiments, the base pairing region between the tracrRNA anti-repeat sequence and the CRISPR repeat sequence is 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 , 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or more nucleotides in length. In certain embodiments, the anti-repeat region of a tracrRNA that is fully or partially complementary to a CRISPR repeat sequence is about 10 nucleotides in length. In certain embodiments, the anti-repeat region of a tracrRNA that is fully or partially complementary to a CRISPR repeat sequence is 10 nucleotides in length. In some embodiments, the degree of complementarity between a CRISPR repeat sequence and its corresponding tracrRNA anti-repeat sequence when optimally aligned using a suitable alignment algorithm is between 50% and 99% or greater, such as but not limited to about 50%. , about 60%, about 70%, about 75%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more. In certain embodiments, the degree of complementarity between a CRISPR repeat sequence and its corresponding tracrRNA anti-repeat sequence when optimally aligned using a suitable alignment algorithm is 50%, 60%, 70%, 75%, 80%, 81 %, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more.

In various embodiments, the entire tracrRNA comprises between about 60 nucleotides and greater than about 210 nucleotides. In certain embodiments, the entire tracrRNA comprises between 60 nucleotides and greater than 210 nucleotides. For example, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, about 100, about 105, about 110, about 115, about 120, about 125, about 130 , about 135, about 140, about 150, about 160, about 170, about 180, about 190, about 200, about 210 or more nucleotides in length. In certain embodiments, the tracrRNA is 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 150, 160, 170, 180, 190 , 200, 210 or more nucleotides in length. In certain embodiments, the tracrRNA is about 100 to about 210 nucleotides in length, such as about 95, about 96, about 97, about 98, about 99, about 100, about 105, about 106, about 107, about 108, about 109, and about 100 nucleotides in length. In certain embodiments, the tracrRNA is 100 to 110 nucleotides in length, including 95, 96, 97, 98, 99, 100, 105, 106, 107, 108, 109 and 110 nucleotides in length.

The guide RNA forms a complex with an RNA-guided, DNA-binding polypeptide or an RNA-guided nuclease to direct the RNA-guided nuclease to bind to a target sequence. When the guide RNA complexes with RGN, the bound RGN introduces single-stranded or double-stranded breaks in the target sequence. After the target sequence is cleaved, the break can be repaired such that the DNA sequence of the target sequence is modified during the repair process. Provided herein are methods of using mutant variants of an RNA-guided nuclease that is a nuclease inactive or nickase linked to deaminase to modify a target sequence in the DNA of a host cell. Mutant variants of RNA-guided nucleases in which nuclease activity is inactivated or significantly reduced may be referred to as RNA-guided, DNA-binding polypeptides, in which the polypeptide is able to bind a target sequence but must Because there is no need to cut it. RNA-guided nucleases capable of cleaving only a single strand of a double-stranded nucleic acid molecule are referred to herein as nickases.

The target nucleotide sequence is bound by the RNA-guided, DNA-binding polypeptide and hybridizes with the guide RNA associated with RGDBP. The target sequence can then be subsequently cleaved if RGDBP retains nuclease activity (ie, RGN) encompassing its activity as a nickase.

The guide RNA may be a single guide RNA or a dual-guide RNA system. A single guide RNA comprises a crRNA and optionally a tracrRNA on a single molecule of RNA, whereas a dual-guide RNA system comprises a crRNA and tracrRNA present on two separate RNA molecules, which are part of the CRISPR repeat sequence of the crRNA. and hybridizes to each other through at least a portion of the tracrRNA, which may be fully or partially complementary to the CRISPR repeat sequence of the crRNA. In some of these embodiments where the guide RNA is a single guide RNA, the crRNA and optionally the tracrRNA are separated by a linker nucleotide sequence.

Generally, the linker nucleotide sequence is one that does not contain complementary bases to avoid formation of secondary structure comprising nucleotides in or within the linker nucleotide sequence. In some embodiments, the linker nucleotide sequence between the crRNA and the tracrRNA is at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12 or more nucleotides in length am. In certain embodiments, the linker nucleotide sequence between the crRNA and tracrRNA is 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more nucleotides in length. In certain embodiments, the linker nucleotide sequence of a single guide RNA is at least 4 nucleotides in length. In certain embodiments, the linker nucleotide sequence of a single guide RNA is 4 nucleotides in length.

In certain embodiments, guide RNAs can be introduced into target cells, organelles, or embryos as RNA molecules. Guide RNAs can be transcribed in vitro or chemically synthesized. In some embodiments, a nucleotide sequence encoding a guide RNA is introduced into a cell, organelle, or embryo. In some embodiments, a nucleotide sequence encoding a guide RNA is operably linked to a promoter (eg, RNA polymerase III promoter). A promoter may be heterologous to a native promoter or to a guide RNA-encoding nucleotide sequence.

In various embodiments, a guide RNA can be introduced into a target cell, organelle, or embryo as a ribonucleoprotein complex as described herein, and the guide RNA binds to an RNA-guided nuclease polypeptide.

The guide RNA directs the associated RNA-guided nuclease to a specific target nucleotide sequence of interest through hybridization of the guide RNA to the target nucleotide sequence. The target nucleotide sequence may include DNA, RNA, or a combination of both, and may be single-stranded or double-stranded. The target nucleotide sequence can be genomic DNA (ie, chromosomal DNA), plasmid DNA, or an RNA molecule (eg, messenger RNA, ribosomal RNA, transfer RNA, micro RNA, small interfering RNA). A target nucleotide sequence may be bound (and in some embodiments cleaved) by an RNA-guided, DNA-binding polypeptide in vitro or in a cell. Chromosomal sequences targeted by RGDBP can be nuclear, plastid or mitochondrial chromosomal sequences. In some embodiments, a target nucleotide sequence is unique in a target genome.

In some embodiments, the target nucleotide sequence is adjacent to a protospacer adjacent motif (PAM). PAMs are generally about 1 to about 10 nucleotides from the target nucleotide sequence (about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, or about 10 from the target nucleotide sequence). nucleotides). In certain embodiments, the PAM is within 1 to 10 nucleotides from the target nucleotide sequence, including 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 nucleotides from the target nucleotide sequence. A PAM may be 5' or 3' of a target sequence. In some embodiments, the PAM is 3' of the target sequence. Generally, a PAM is a consensus sequence of about 2-6 nucleotides, but in certain embodiments is 1, 2, 3, 4, 5, 6, 7, 8, 9 or more nucleotides in length.

A PAM limits the sequence that a given RGDBP or RGN can target because its PAM needs to be in proximity to the target nucleotide sequence. Upon recognizing its corresponding PAM sequence, RGN can cleave the target nucleotide sequence at a specific cleavage site. As used herein, a cleavage site consists of two specific nucleotides within a target nucleotide sequence between which the nucleotide sequence is cleaved by the RGN. The cleavage sites are 1st and 2nd, 2nd and 3rd, 3rd and 4th, 4th and 5th, 5th and 6th, 7th and 8th, or 8th from the PAM in the 5' or 3' direction. It may include the th and ninth nucleotides. Because RGNs can cleave target nucleotide sequences to create staggered ends, in some embodiments, the cleavage site is a distance of 2 nucleotides from the PAM on the positive (+) strand of the polynucleotide and the negative (-) strand of the polynucleotide. It is defined based on the distance of 2 nucleotides from the PAM of the phase.

RGDBP and RGN can be used to deliver fused polypeptides, polynucleotides, or small molecule payloads to specific genomic locations.

In embodiments where the DNA-binding polypeptide comprises a meganuclease, the target sequence may include a pair of inverted 9 base pair “half sites” separated by 4 base pairs. For single-chain meganucleases, the N-terminal domain of the protein contacts the first half-site and the C-terminal domain of the protein contacts the second half-site. Cleavage by meganuclease produces a 4 base pair 3' overhang. In embodiments where the DNA-binding polypeptide comprises a dense TALEN, the recognition sequence is a first CNNNGN sequence recognized by the I-TevI domain, followed by a non-specific spacer of 4-16 base pairs in length, followed by a TAL-effector and a second sequence of 16-22 bp in length recognized by the domain (this sequence typically has a 5' T base). In embodiments where the DNA-binding polypeptide comprises zinc fingers, the DNA binding domain typically comprises an 18-bp recognition sequence comprising a pair of 9 base pair "half-sites" separated by 2-10 base pairs. , and cleavage by nucleases produces blunt ends or 5' overhangs of variable length (frequently 4 base pairs).

IV. fusion protein

In some embodiments, a DNA-binding polypeptide (eg, a nuclease-inactive or nickase RGN) is operably linked to a deaminase of the invention. In some embodiments, a DNA-binding polypeptide (e.g., nuclease inactive RGN or nickase RGN) fused to a deaminase of the invention can be targeted to a specific location on a nucleic acid molecule (i.e., a target nucleic acid molecule). , which in some embodiments is a specific genomic locus to alter the expression of a sequence of interest. In some embodiments, binding of the fusion protein to the target sequence results in deamination of the nucleobases, resulting in a switch from one nucleobase to another. In some embodiments, binding of such fusion proteins to a target sequence results in deamination of nucleobases adjacent to the target sequence. Nucleobases flanking the target sequence that are deaminated and mutated using the compositions and methods disclosed herein are 1, 2, 3, 4 from the 5' or 3' end of the target sequence (bound by the gRNA) within the target nucleic acid molecule. , 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65 , 70, 75, 80, 85, 90, 95, or 100 base pairs. Some aspects of the present disclosure include (i) DNA-binding polypeptides (eg, nuclease-inactive or nickase RGN polypeptides); (ii) a deaminase polypeptide; and optionally (iii) a second deaminase. The second deaminase can be the same deaminase as the first deaminase or it can be a different deaminase. In some embodiments, both the first and second deaminase are adenine deaminase of the invention.

The present disclosure provides fusion proteins of various configurations. In some embodiments, the deaminase polypeptide is fused to the N-terminus of a DNA-binding polypeptide (eg, an RGN polypeptide). In some embodiments, the deaminase polypeptide is fused to the C-terminus of a DNA-binding polypeptide (eg, an RGN polypeptide).

In some embodiments, the deaminase and DNA-binding polypeptide (eg, RNA-guided, DNA-binding polypeptide) are fused to each other via a peptide linker. A linker between a deaminase and a DNA-binding polypeptide (e.g., RNA-guided, DNA-binding polypeptide) determines the editing window of the fusion protein, thereby increasing deaminase specificity and avoiding off-target mutations. can reduce Deaminase for specific applications using a variety of linker lengths and flexibility ranging from very flexible linkers of types (GGGGS) _n and (G) _n to more rigid linkers of types (EAAAK) _n and (XP) _n Optimal length and stiffness for activity can be achieved. As used herein, the term “linker” refers to a chemical group or molecule that connects two molecules or moieties, eg, a binding domain and a cleavage domain of a nuclease. In some embodiments, a linker connects an RNA guided nuclease and a deaminase. In some embodiments, a linker connects a malfunctioning or inactive RGN and a deaminase. In a further embodiment, a linker connects two deaminase. Typically, a linker is positioned between, or flanked by, two groups, molecules or other moieties, and connects the two to each other via a covalent bond. In some embodiments, a linker is an amino acid or a plurality of amino acids (eg, a peptide or protein). In some embodiments, a linker is an organic molecule, group, polymer, or chemical moiety. In some embodiments, a linker is 3-100 amino acids in length, for example 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 , 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 30-35, 35-40, 40-45, 45-50, 50-60, 60-70, 70-80 , 80-90, 90-100, 100-150, or 150-200 amino acids in length. Longer or shorter linkers are also contemplated. In some embodiments, shorter linkers are preferred to reduce the overall size or length of the fusion protein or its coding sequence.

In some embodiments, a linker comprises a (GGGGS) _n , (G) _n , (EAAAK) _n , or (XP) _n motif, or a combination of any of these, where n is independently an integer from 1 to 30. am. In some embodiments, n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29 or 30, or more than one linker or more than one linker motif if present, any combination thereof. Additional suitable linker motifs and linker configurations will be apparent to those skilled in the art. In some embodiments, suitable linker motifs and configurations include those described by Chen et al., 2013 (Adv Drug Deliv Rev. 65(10):1357-69, the entire contents of which are incorporated herein by reference). . Additional suitable linker sequences will be apparent to those skilled in the art. In some embodiments, the linker sequence comprises the amino acid sequence set forth in SEQ ID NO: 45 or 442.

In some embodiments, the general architecture of an exemplary fusion protein provided herein has the structure: [NH ₂ ]-[deaminase]-[DBP]-[COOH]; [NH ₂ ]-[DBP]-[deaminase]-[COOH]; [NH ₂ ]-[DBP]-[deaminase]-[deaminase]-[COOH]; [NH ₂ ]-[deaminase]-[DBP]-[deaminase]-[COOH]; or [NH ₂ ]-[deaminase]-[deaminase]-[DBP]-[COOH], wherein DBP is a DNA-binding polypeptide, NH ₂ is the N-terminus of the fusion protein, and COOH is the C-terminus of the fusion protein. In some embodiments, the fusion protein comprises more than two deaminase polypeptides.

In certain embodiments, the general architecture of exemplary fusion proteins provided herein has the structure: [NH ₂ ]-[deaminase]-[RGN]-[COOH]; [NH ₂ ]-[RGN]-[deaminase]-[COOH]; [NH ₂ ]-[RGN]-[deaminase]-[deaminase]-[COOH]; [NH ₂ ]-[deaminase]-[RGN]-[deaminase]-[COOH]; or [NH ₂ ]-[deaminase]-[deaminase]-[RGN]-[COOH], wherein NH ₂ is the N-terminus of the fusion protein and COOH is the C-terminus of the fusion protein. . In some embodiments, the fusion protein comprises more than two deaminase polypeptides.

In some embodiments, the fusion protein has the structure: [NH ₂ ]-[deaminase]-[nuclease-inactive RGN]-[COOH]; [NH ₂ ]-[deaminase]-[deaminase]-[nuclease-inactive RGN]-[COOH]; [NH ₂ ]-[nuclease-inactive RGN]-[deaminase]-[COOH]; [NH ₂ ]-[deaminase]-[nuclease-inactive RGN]-[deaminase]-[COOH]; or [NH ₂ ]-[nuclease-inactive RGN]-[deaminase]-[deaminase]-[COOH]. "Nuclease-inactive RGN" should be understood to refer to any RGN, including any CRISPR-Cas protein that has been mutated to be nuclease-inactive. In some embodiments, the fusion protein comprises more than two deaminase polypeptides.

In some embodiments, the fusion protein has the structure: [NH ₂ ]-[deaminase]-[RGN nickase]-[COOH]; [NH ₂ ]-[deaminase]-[deaminase]-[RGN nickase]-[COOH]; [NH ₂ ]-[RGN nickase]-[deaminase]-[COOH]; [NH ₂ ]-[deaminase]-[RGN nickase]-[deaminase]-[COOH]; or [NH ₂ ]-[RGN nickase]-[deaminase]-[deaminase]-[COOH]. "RGN nickase" should be understood to refer to any RGN, including any CRISPR-Cas protein that has been mutated to be active as a nickase.

In some embodiments, "-" used in the general architecture above indicates the presence of an optional linker sequence. In some embodiments, a fusion protein provided herein does not include a linker sequence. In some embodiments, at least one of the optional linker sequences is present.

Other exemplary features that may be present are localization sequences, such as nuclear localization sequences, cytoplasmic localization sequences, export sequences, such as nuclear export sequences, or other localization sequences, as well as sequences useful for solubilization, purification, or detection of fusion proteins. It is a tag. Suitable localization signal sequences and sequences of protein tags provided herein include biotin carboxylase carrier protein (BCCP) tag, myc-tag, calmodulin-tag, FLAG-tag, hemagglutinin (HA)-tag, histidine. polyhistidine tag, also referred to as tag or His-tag, maltose binding protein (MBP)-tag, nus-tag, glutathione-S-transferase (GST)-tag, green fluorescent protein (GFP)-tag, thiourea including, but not limited to, Doxin-Tag, S-Tag, SofTag (e.g., SofTag 1, SofTag 3), StrepTag, Biotin Ligase Tag, FlAsH Tag, V5 Tag, and SBP-Tag. . Additional suitable sequences will be apparent to those skilled in the art.

In certain embodiments, a fusion protein disclosed herein comprises at least one cell-penetrating domain that facilitates cellular uptake of the fusion protein. Cell-penetrating domains are known in the art and generally consist of positively charged amino acid residues (i.e., polycationic cell-penetrating domains), alternating polar amino acid residues and non-polar amino acid residues (i.e., amphiphilic cell-penetrating domains). penetrating domain), or stretches of hydrophobic amino acid residues (ie, hydrophobic cell-penetrating domain) (see, eg, Milletti F. (2012) Drug Discov Today 17:850-860). A non-limiting example of a cell-penetrating domain is the trans-activating transcriptional activator (TAT) from human immunodeficiency virus 1.

In some embodiments, a deaminase or fusion protein provided herein further comprises a nuclear localization sequence (NLS). The nuclear localization signal, the plastid localization signal, the mitochondrial localization signal, the dual-targeting localization signal, and/or the cell-penetrating domain may be amino-terminal (N-terminal), carboxyl-terminal (C-terminal), or It may be located at an internal location of the fusion protein.

In some embodiments, the NLS is fused to the N-terminus of the fusion protein or deaminase. In some embodiments, the NLS is fused to the C-terminus of a fusion protein or deaminase. In some embodiments, the NLS is fused to the N-terminus of the deaminase of the fusion protein. In some embodiments, the NLS is fused to the C-terminus of the deaminase of the fusion protein. In some embodiments, the NLS is fused to the N-terminus of a DNA-binding polypeptide (eg, RGN polypeptide) of the fusion protein. In some embodiments, the NLS is fused to the C-terminus of a DNA-binding polypeptide (eg, RGN polypeptide) of the fusion protein. In some embodiments, the NLS is fused to the N-terminus of the deaminase polypeptide of the fusion protein. In some embodiments, the NLS is fused to the C-terminus of the deaminase polypeptide of the fusion protein. In some embodiments, the NLS is fused to the fusion protein via one or more linkers. In some embodiments, the NLS is fused to a fusion protein without a linker. In some embodiments, the NLS comprises the amino acid sequence of any one of the NLS sequences provided or referenced herein. In some embodiments, the NLS comprises an amino acid sequence as set forth in SEQ ID NO:43 or SEQ ID NO:46. In some embodiments, the fusion protein or deaminase comprises SEQ ID NO: 43 on its N-terminus and SEQ ID NO: 46 on its C-terminus.

In some embodiments, a fusion protein as provided herein comprises a full-length sequence of a deaminase, eg, any one of SEQ ID NOs: 1-10 and 399-441. However, in some embodiments, a fusion protein as provided herein does not include the full-length sequence of a deaminase, but only fragments thereof. For example, in some embodiments, a fusion protein provided herein further comprises a DNA-binding polypeptide (eg, RNA-guided, DNA-binding) domain and a deaminase domain.

In some embodiments, a fusion protein of the invention comprises a DNA-binding polypeptide (eg, RGN) and a deaminase, wherein the deaminase is to any of SEQ ID NOs: 1-10 and 399-441 at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least have an amino acid sequence that has 98%, at least 99% or 100% identity. Examples of such fusion proteins are described in the Examples section herein.

In some embodiments, the fusion protein comprises one deaminase polypeptide. In some embodiments, the fusion protein comprises at least two deaminase polypeptides operably linked, either directly or through a peptide linker. In some embodiments, the fusion protein comprises one deaminase polypeptide and a second deaminase polypeptide is co-expressed with the fusion protein.

Also provided herein is a ribonucleoprotein complex comprising a fusion protein comprising a deaminase and RGDBP, and a guide RNA as a single guide or dual guide RNA (collectively also referred to as gRNA).

V. Nucleotides Encoding Deaminase, Fusion Proteins, and/or gRNAs

The present disclosure provides polynucleotides (SEQ ID NOs: 11-20 and 443-485) encoding the deaminase polypeptides disclosed herein. The present disclosure further provides polynucleotides encoding fusion proteins comprising deaminase and DNA-binding polypeptides such as meganucleases, zinc finger fusion proteins or TALENs. The present disclosure further provides a polynucleotide encoding a fusion protein comprising a deaminase domain and an RNA-guided, DNA-binding polypeptide. Such RNA-guided, DNA-binding polypeptides may be RGNs or RGN variants. Protein variants may be nuclease-inactive or nickase. RGN can be a CRISPR-Cas protein or an active variant or fragment thereof. SEQ ID NOs: 41 and 42 are non-limiting examples of RGN and nickase RGN variants, respectively. Examples of CRISPR-Cas nucleases are well known in the art, and similar corresponding mutations can also generate mutant variants that are either nickases or are nuclease inactive.

One embodiment of the invention provides a polynucleotide encoding a fusion protein comprising RGDBP and a deaminase described herein (SEQ ID NOs: 1-10 and 399-441, or variants thereof). In some embodiments, the second polynucleotide encodes a guide RNA required by RGDBP to target a nucleotide sequence of interest. In some embodiments, the guide RNA and fusion protein are encoded by the same polynucleotide.

Use of the term "polynucleotide" is not intended to limit the present disclosure to polynucleotides comprising DNA, but such DNA polynucleotides are contemplated. One skilled in the art will know that polynucleotides can include ribonucleotides (RNA) and combinations of ribonucleotides and deoxyribonucleotides. These deoxyribonucleotides and ribonucleotides include both naturally occurring molecules and synthetic analogs. Polynucleotides disclosed herein also encompass all forms of sequence, including but not limited to single-stranded forms, double-stranded forms, stem-and-loop structures, circular forms (including circular RNA), etc. do.

One embodiment of the present invention is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80% relative to any of SEQ ID NOs: 11-20 and 443-485. , at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity, wherein the nucleic acid molecule comprises an adenine deaminase Encodes an active deaminase. A nucleic acid molecule may further include a heterologous promoter or terminator. The nucleic acid molecule may encode a fusion protein, wherein the encoded deaminase is operably linked to a DNA-binding polypeptide and optionally a second deaminase. In some embodiments, the nucleic acid molecule encodes a fusion protein, wherein the encoded deaminase is operably linked to the RGN and optionally a second deaminase.

In some embodiments, a nucleic acid molecule comprising a polynucleotide encoding a deaminase of the invention is codon optimized for expression in an organism of interest. A “codon-optimized” coding sequence is a polynucleotide coding sequence that has its codon usage designed to mimic the preferred codon usage or transcriptional conditions of a particular host cell. Expression in a particular host cell or organism is enhanced as a result of altering one or more codons at the nucleic acid level such that the translated amino acid sequence remains unchanged. Nucleic acid molecules can be entirely or partially codon optimized. Codon tables and other references providing preference information for a wide range of organisms are available in the art (see, for example, Campbell and Gowri (1990) Plant Physiol. 92 for a discussion of plant-preferred codon usage). 1-11]). Methods for synthesizing plant-preferred genes are available in the art. See, for example, US Pat. Nos. 5,380,831, and 5,436,391, and Murray et al. (1989) Nucleic Acids Res. 17:477-498 (incorporated herein by reference).

In some embodiments, a polynucleotide encoding a deaminase, fusion protein, and/or gRNA described herein is provided in an expression cassette for in vitro expression or expression in a cell, organelle, embryo, or organism of interest. The cassette is operably linked to a deaminase provided herein, and/or a fusion protein comprising a deaminase, an RNA-guided DNA-binding polypeptide, and optionally a second deaminase, and/or a polynucleotide encoding a gRNA. It may include linked 5' and 3' regulatory sequences, which allow expression of the polynucleotide. The cassette may further contain at least one additional gene or genetic element that is co-transformed into the organism. When additional genes or elements are included, the components are operably linked. The term "operably linked" is intended to mean a functional connection between two or more elements. For example, an operable linkage between a promoter and a coding region of interest (eg, a region encoding a deaminase, an RNA-guided DNA-binding polypeptide, and/or a gRNA) is a functional linkage that allows expression of the coding region of interest. It is a connection. The operably connected elements may or may not be contiguous. When used to refer to the joining of two protein coding regions, operably linked means that the coding regions are in the same reading frame. In some embodiments, additional gene(s) or element(s) are provided on multiple expression cassettes. For example, a nucleotide sequence encoding a deaminase disclosed herein, either alone or as a component of a fusion protein, may be present on one expression cassette, whereas a nucleotide sequence encoding a gRNA may be present on a separate expression cassette. can Another example is a nucleotide sequence encoding a deaminase disclosed herein alone on a first expression cassette, a nucleotide sequence encoding a gRNA on a second expression cassette encoding a fusion protein comprising the deaminase, and a nucleotide sequence encoding a gRNA on a third expression cassette. can have a sequence. Such expression cassettes are provided with a plurality of restriction sites and/or recombination sites for insertion of polynucleotides under the transcriptional control of regulatory regions. Expression cassettes containing selectable marker genes may also be present.

The expression cassette comprises a transcriptional (and, in some embodiments, translation) initiation region (i.e., a promoter) that is functional in the organism of interest in the 5′-3′ transcriptional direction, a deaminase-encoding polynucleotide of the invention, and a transcriptional (and In some embodiments, a translational) termination region (ie, termination region). A promoter of the present invention can direct or drive the expression of a coding sequence in a host cell. Regulatory regions (eg, promoters, transcriptional regulatory regions, and translational termination regions) may be endogenous or heterologous to the host cell or to each other. "Heterologous," as used herein with reference to a sequence, is a sequence that originates from a foreign species or, if originating from the same species, has been substantially modified from its native form in composition and/or genomic locus by intentional human intervention. As used herein, a chimeric gene comprises a coding sequence operably linked to a transcription initiation region that is heterologous to the coding sequence.

A convenient closing area is a. Ti-plasmids of A. tumefaciens , such as the octopine synthase and nopaline synthase termination regions. Also, see Guerineau et al. (1991) Mol. Gen. Genet. 262:141-144; Proudfoot (1991) Cell 64:671-674; Sanfacon et al. (1991) Genes Dev. 5:141-149; Mogen et al. (1990) Plant Cell 2:1261-1272; Munroe et al. (1990) Gene 91:151-158; Ballas et al. (1989) Nucleic Acids Res. 17:7891-7903; and Joshi et al. (1987) Nucleic Acids Res. 15:9627-9639].

Additional regulatory signals include, but are not limited to, transcription initiation start sites, operators, activators, enhancers, other regulatory elements, ribosome binding sites, initiation codons, termination signals, and the like. See, for example, U.S. Patent Nos. 5,039,523 and 4,853,331; EPO 0480762A2; See Sambrook et al. (1992) Molecular Cloning: A Laboratory Manual, ed. Maniatis et al. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.)], hereinafter "Sambrook 11"; See Davis et al., eds. (1980) Advanced Bacterial Genetics (Cold Spring Harbor Laboratory Press), Cold Spring Harbor, N.Y.], and the references cited therein.

To prepare an expression cassette, various DNA fragments can be engineered to provide DNA sequences in the proper orientation and, where appropriate, in the proper reading frame. To this end, adapters or linkers may be used to join the DNA fragments, or other manipulations may be involved to provide convenient restriction sites, removal of unnecessary DNA, removal of restriction sites, and the like. For this purpose, in vitro mutagenesis, primer repair, restriction, annealing, resubstitution, such as transfer and conversion may be involved.

Numerous promoters can be used in the practice of the present invention. Promoters can be selected based on the desired outcome. Nucleic acids can be constitutive, inducible, growth stage-specific, cell type-specific, tissue-preferred, tissue-specific, or combined with other promoters for expression in the organism of interest. See, for example, WO 99/43838, and U.S. Patent Nos. 8,575,425; 7,790,846; 8,147,856; 8,586832; 7,772,369; 7,534,939; 6,072,050; 5,659,026; 5,608,149; 5,608,144; 5,604,121; 5,569,597; 5,466,785; 5,399,680; 5,268,463; 5,608,142; and 6,177,611; These are incorporated herein by reference.

For expression in plants, constitutive promoters may also include the CaMV 35S promoter (Odell et al. (1985) Nature 313:810-812); rice actin (McElroy et al. (1990) Plant Cell 2:163-171); ubiquitin (Christensen et al. (1989) Plant Mol. Biol. 12:619-632 and Christensen et al. (1992) Plant Mol. Biol. 18:675-689); pEMU (Last et al. (1991) Theor. Appl. Genet. 81:581-588); and MAS (Velten et al. (1984) EMBO J. 3:2723-2730).

Examples of inducible promoters are the Adhl promoter inducible by hypoxia or cold stress, the Hsp70 promoter inducible by heat stress, the PPDK promoter and the pepcarboxylase promoter both inducible by light. Chemically inducible promoters such as the relaxant-derived In2-2 promoter (U.S. Patent No. 5,364,780), the auxin-inducible and rugosa specific but also active Axig1 promoter in callus (PCT US01/22169), the steroid-responsive promoter (e.g. , the estrogen-induced ERE promoter, and Schena et al. (1991) Proc. Natl. Acad. Sci. USA 88:10421-10425 and McNellis et al. (1998) Plant J. 14(2):247-257 ]) and the tetracycline-inducible and tetracycline-repressible promoters (see, e.g., Gatz et al. (1991) Mol. Gen. Genet. 227:229- 237], and US Pat. Nos. 5,814,618 and 5,789,156), incorporated herein by reference, are also useful.

In some embodiments, a tissue-specific or tissue-preferred promoter is used to target expression of an expression construct within a particular tissue. In certain embodiments, a tissue-specific or tissue-preferred promoter is active in plant tissue. Examples of promoters under developmental control in plants include promoters that preferentially initiate transcription in certain tissues, such as leaves, roots, fruits, seeds or flowers. A “tissue specific” promoter is a promoter that initiates transcription only in a specific tissue. Unlike constitutive expression of a gene, tissue-specific expression is the result of multiple, interactive levels of gene regulation. Thus, promoters from homologous or closely related plant species can preferably be used to achieve efficient and reliable expression of the transgene in specific tissues. In some embodiments, expression includes a tissue-preferred promoter. A "tissue-preferred" promoter is a promoter that initiates transcription preferentially, but not necessarily entirely or singly, in a particular tissue.

In some embodiments, a nucleic acid molecule encoding a deaminase described herein includes a cell type-specific promoter. A “cell type specific” promoter is a promoter that primarily directs expression in a particular cell type of one or more organs. Some examples of plant cells in which cell type specific promoters that are functional in plants may be primarily active include, for example, BETL cells, roots, vascular cells in leaves, stipe cells, and stem cells. A nucleic acid molecule may also include a cell type preferred promoter. A “cell type preferred” promoter is a promoter that primarily, but not necessarily entirely or solely, directs expression in a particular cell type of one or more organs. Some examples of plant cells in which cell type-preferred promoters that are functional in plants may be preferentially active include, for example, BETL cells, roots, vascular cells in leaves, stipe cells, and stem cells.

In some embodiments, a nucleic acid sequence encoding a deaminase, fusion protein and/or gRNA is operably linked to a promoter sequence recognized by phage RNA polymerase, eg, for in vitro mRNA synthesis. In such embodiments, in vitro-transcribed RNA can be purified for use in the methods described herein. For example, the promoter sequence can be a T7, T3, or SP6 promoter sequence or a variant of the T7, T3, or SP6 promoter sequence. In such embodiments, the expressed protein and/or RNA may be purified for use in the genomic modification methods described herein.

In certain embodiments, a polynucleotide encoding a deaminase, fusion protein, and/or gRNA is a polyadenylation signal (e.g., the SV40 polyA signal and other signals functional in plants) and/or at least one transcriptional termination. connected to the sequence. In some embodiments, the sequence encoding the deaminase or fusion protein comprises at least one nuclear localization signal capable of trafficking the protein to a specific subcellular location, at least one cell-penetrating signal, as described elsewhere herein. domain and/or sequence(s) encoding at least one signal peptide.

In some embodiments, the polynucleotide encoding the deaminase, fusion protein and/or gRNA is in a vector or multiple vectors. "Vector" refers to a polynucleotide composition for transporting, transferring or introducing a nucleic acid into a host cell. Suitable vectors include plasmid vectors, phagemids, cosmids, artificial/mini-chromosomes, transposons, and viral vectors (eg, lentiviral vectors, adeno-associated viral vectors, baculovirus vectors). In some embodiments, the vector may contain additional expression control sequences (eg, enhancer sequences, Kozak sequences, polyadenylation sequences, transcription termination sequences), selectable marker sequences (eg, antibiotic resistance genes), origins of replication, and the like. include Additional information may be found in "Current Protocols in Molecular Biology" Ausubel et al., John Wiley & Sons, New York, 2003 or "Molecular Cloning: A Laboratory Manual" Sambrook & Russell, Cold Spring Harbor Press, Cold Spring Harbor, N.Y. , 3rd edition, 2001].

In some embodiments, the vector includes a selectable marker gene for selection of transformed cells. Selectable marker genes are used for selection of transformed cells or tissues. Marker genes include genes encoding antibiotic resistance, such as genes encoding neomycin phosphotransferase II (NEO) and hygromycin phosphotransferase (HPT), as well as herbicidal compounds such as glufosinate ammonium, bromox It contains genes conferring resistance to cynyl, imidazolinone and 2,4-dichlorophenoxyacetate (2,4-D).

In some embodiments, an expression cassette or vector comprising a sequence encoding a fusion protein comprising an RNA-guided DNA-binding polypeptide, such as RGN, further comprises a sequence encoding a gRNA. In some embodiments, the sequence(s) encoding a gRNA is operably linked to at least one transcriptional control sequence for expression of the gRNA in an organism or host cell of interest. For example, a polynucleotide encoding a gRNA can be operably linked to a promoter sequence recognized by RNA polymerase III (Pol III). Examples of suitable Pol III promoters include, but are not limited to, the mammalian U6, U3, H1, and 7SL RNA promoters and the rice U6 and U3 promoters.

As shown, expression constructs comprising nucleotide sequences encoding deaminase, fusion proteins and/or gRNAs can be used to transform organisms of interest. Transformation methods involve introducing a nucleotide construct into an organism of interest. "Introducing" is intended to introduce a nucleotide construct into a host cell in such a way that the construct gains access to the interior of the host cell. The method of the present invention does not require a specific method to introduce the nucleotide construct into the host organism, only the nucleotide construct needs access to the interior of at least one cell of the host organism. Host cells may be eukaryotic or prokaryotic. In certain embodiments, eukaryotic host cells are plant cells, mammalian cells, or insect cells. Methods for introducing nucleotide constructs into plants and other host cells are known in the art, including, but not limited to, stable transformation methods, transient transformation methods, and virus-mediated methods.

The methods produce transformed organisms, such as whole plants, as well as plants, including plant organs (eg, leaves, stems, roots, etc.), seeds, plant cells, propagules, embryos and their progeny. Plant cells can be differentiated or undifferentiated (eg, callus, suspension cultured cells, protoplasts, leaf cells, root cells, phloem cells, pollen).

A "transgenic organism" or "transformed organism" or "stably transformed" organism or cell or tissue refers to an organism into which a polynucleotide encoding a deaminase of the present invention has been incorporated or integrated. It is recognized that other exogenous or endogenous nucleic acid sequences or DNA fragments may also be incorporated into the host cell. Agrobacterium- and biolistic-mediated transformation remain the two predominantly used approaches for transformation of plant cells. However, transformation of host cells can be accomplished by infection, transfection, microinjection, electroporation, microprojection, biolistic or particle bombardment, electroporation, silica/carbon fiber, ultrasound-mediated, PEG-mediated, calcium phosphate co-precipitation, polycation DMSO technology, DEAE dextran procedure, and viral mediation, liposomal mediation, and the like. Virus-mediated introduction of polynucleotides encoding deaminase, fusion proteins and/or gRNAs can be retrovirus, lentivirus, adenovirus and adeno-associated virus mediated introduction and expression, as well as colimoviruses (eg, coli flower mosaic virus), geminiviruses (eg soybean golden yellow mosaic virus or maize stripe virus) and RNA plant viruses (eg tobacco mosaic virus).

Transformation protocols, as well as protocols for introducing polypeptide or polynucleotide sequences into plants, can vary depending on the type of host cell targeted for transformation (eg, monocotyledonous or dicotyledonous plant cells). Transformation methods are known in the art and are described in U.S. Patent Nos.: 8,575,425; 7,692,068; 8,802,934; 7,541,517, each of which is incorporated herein by reference. See also Rakoczy-Trojanowska, M. (2002) Cell Mol Biol Lett. 7:849-858; Jones et al. (2005) Plant Methods 1:5; Rivera et al. (2012) Physics of Life Reviews 9:308-345; Bartlett et al. (2008) Plant Methods 4:1-12; Bates, G.W. (1999) Methods in Molecular Biology 111:359-366; Binns and Thomashow (1988) Annual Reviews in Microbiology 42:575-606; Christou, P. (1992) The Plant Journal 2:275-281; Christou, P. (1995) Euphytica 85:13-27; Tzfira et al. (2004) TRENDS in Genetics 20:375-383; Yao et al. (2006) Journal of Experimental Botany 57:3737-3746; Zupan and Zambryski (1995) Plant Physiology 107:1041-1047; Jones et al. (2005) Plant Methods 1:5].

Transformation can result in stable or transient incorporation of the nucleic acid into the cell. "Stable transformation" is intended to mean that a nucleotide construct introduced into a host cell is integrated into the host cell's genome and can be inherited by its progeny. "Transient transformation" is intended to mean that the polynucleotide is introduced into a host cell and is not integrated into the genome of the host cell.

Methods for transforming chloroplasts are known in the art. See, eg, Svab et al. (1990) Proc. Natl. Acad. Sci. USA 87:8526-8530; Svab and Maliga (1993) Proc. Natl. Acad. Sci. USA 90:913-917; Svab and Maliga (1993) EMBO J. 12:601-606. The method relies on particle gun delivery of DNA containing a selectable marker, and targeting of the DNA to the plastid genome via homologous recombination. Additionally, plastid transformation can be achieved by transactivation of a silent plastid-mediated transgene by tissue-preferred expression of nuclear-encoded and plastid-directed RNA polymerase. Such a system is described in McBride et al. (1994) Proc. Natl. Acad. Sci. USA 91:7301-7305].

Transformed cells can be grown into transgenic organisms, such as plants, according to conventional methods. See, eg, McCormick et al. (1986) Plant Cell Reports 5:81-84. These plants can then be grown, pollinated with the same transformed strain or with a different strain, and the resulting hybrids identified with the deaminase or fusion protein polynucleotide. The deaminase or fusion protein polynucleotide may be stably maintained and inherited, and seeds may be harvested and grown for two or more generations to ensure the presence of the deaminase or fusion protein polynucleotide. In this way, the invention provides transformed seeds (also referred to as “transgenic seeds”) having a nucleotide construct of the invention, eg, an expression cassette of the invention, stably incorporated into the genome.

In some embodiments, a transformed cell is introduced into an organism. These cells may originate from an organism, and the cells are transformed in an ex vivo approach.

The sequences provided herein can be used for transformation of any plant species, including but not limited to monocots and dicotyledons. Examples of plants of interest are maize (maize), sorghum, wheat, sunflower, tomato, cruciferous, pepper, potato, cotton, rice, soybean, sugar beet, sugarcane, tobacco, barley, and oilseed rape, Brassica species, alfalfa, Rye, millet, safflower, peanut, sweet potato, cassava, coffee, coconut, pineapple, citrus tree, cocoa, tea, banana, avocado, fig, guava, mango, olive, papaya, cashew, macadamia, almond, oat, vegetable, ornamental plants, and conifers, but are not limited thereto.

Vegetables include, but are not limited to, tomatoes, lettuce, green beans, lima beans, peas, and members of the genus Cucumis, such as cucumbers, cantaloupes, and muskmelons. Ornamental plants include, but are not limited to, azaleas, hydrangeas, hibiscus, roses, tulips, daffodils, petunias, carnations, poinsettias, and chrysanthemums. Preferably, the plant of the present invention is a crop plant (eg, maize, sorghum, wheat, sunflower, tomato, brassicaceae, pepper, potato, cotton, rice, soybean, sugar beet, sugar cane, tobacco, barley, oilseed rape etc.).

As used herein, the term plant refers to plant cells, plant protoplasts, plant cell tissue cultures from which plants can regenerate, plant calli, plant masses, and plants or parts of plants such as embryos, pollen, ovules. , including intact plant cells in seeds, leaves, flowers, branches, fruits, kernels, ears, cobs, hulls, stalks, roots, root tips, anthers, etc. Grain is intended to mean mature seed produced by commercial growers for purposes other than growing or propagating the species. Progeny, variants and mutants of regenerating plants are also included within the scope of the present invention, provided that these portions include the introduced polynucleotide. Additionally, engineered plant products or by-products are provided having the sequences disclosed herein, including, for example, soybean meal.

In some embodiments, polynucleotides encoding deaminase, fusion proteins and/or gRNAs include but are not limited to animals (e.g., mammals, insects, fish, birds, and reptiles), fungi, amoebas, algae, and yeasts. It is used to transform any eukaryotic species, including but not limited to. In some embodiments, the polynucleotide encoding the deaminase, fusion protein and/or gRNA is an archaeal and bacterial (e.g., Bacillus spp ., Klebsiella spp., Streptomyces spp. , Rhizobium Species, Escherichia Species, Pseudomonas Species, Pseudomonas Species, Salmonella Species, Shigella Species, Vibrio Species, Yersinia Species, Myco It is used to transform any prokaryotic species including, but not limited to, Mycoplasma species, Agrobacterium species, Lactobacillus species).

In some embodiments, conventional viral and non-viral based gene transfer methods are used to introduce nucleic acids into mammalian cells or target tissues. Such methods can be used to administer a nucleic acid encoding a deaminase or fusion protein of the invention and optionally a gRNA to cells in culture or in a host organism. Non-viral vector delivery systems include DNA plasmids, RNA (eg, transcripts of vectors described herein), naked nucleic acids, and nucleic acids complexed with delivery vehicles such as liposomes. Viral vector delivery systems include DNA and RNA viruses with episomal or integrated genomes after delivery into cells. Non-limiting examples include colimoviruses (eg, cauliflower mosaic virus), geminiviruses (eg, soybean golden yellow mosaic virus or maize stripe virus), and RNA plant viruses (eg, tobacco mosaic virus). contains the vectors used. For a review of gene therapy procedures, see Anderson, Science 256: 808-813 (1992); Nabel & Feigner, TIBTECH 11:211-217 (1993); Mitani & Caskey, TIBTECH 11:162-166 (1993); Dillon, TIBTECH 11:167-175 (1993); Miller, Nature 357:455-460 (1992); Van Brunt, Biotechnology 6(10): 1149-1154 (1988); Vigne, Restorative Neurology and Neuroscience 8:35-36 (1995); Kremer & Perricaudet, British Medical Bulletin 51(1):31-44 (1995); Haddada et al., in Current Topics in Microbiology and Immunology, Doerfler and Bohm (eds) (1995); and Yu et al., Gene Therapy 1:13-26 (1994).

Non-viral delivery methods of nucleic acids include lipofection, Agrobacterium-mediated transformation, nucleofection, microinjection, biolistics, virosomes, liposomes, immunoliposomes, polycationic or lipid:nucleic acid conjugates, naked DNA, artificial virions, and agent-enhanced uptake of DNA. Lipofection is described in, for example, U.S. Patent Nos. 5,049,386, 4,946,787; and 4,897,355, and lipofection reagents are commercially available (eg, Transfectam™ and Lipofectin™). Suitable cationic and neutral lipids for efficient receptor-recognition lipofection of polynucleotides are described in Feigner, WO 91/17424; including those of WO 91/16024. Delivery can be to cells (eg, in vitro or ex vivo administration) or target tissues (eg, in vivo administration). Preparation of lipid:nucleic acid complexes, including targeted liposomes, such as immunolipid complexes, is well known to those skilled in the art (see, e.g., Crystal, Science 270:404-410 (1995); Blaese et al. al., Cancer Gene Ther.2:291-297 (1995) Behr et al., Bioconjugate Chem.5:382-389 (1994) Remy et al., Bioconjugate Chem. Gao et al., Gene Therapy 2:710-722 (1995) Ahmad et al., Cancer Res. 8, 4,774,085; 4,837,028, and 4,946,787).

The use of RNA or DNA virus-based systems for delivery of nucleic acids utilizes highly evolved processes for targeting viruses to specific cells within the body and trafficking viral payloads into the nucleus. Viral vectors can be administered directly to a patient (in vivo) or can be used to treat cells in vitro, optionally modified cells can be administered to a patient (ex vivo). Conventional viral based systems may include retroviral, lentiviral, adenoviral, adeno-associated and herpes simplex virus vectors for gene delivery. Integration in the host genome is possible by retroviral, lentiviral, and adeno-associated viral gene transfer methods, which often result in long-term expression of the inserted transgene. Additionally, high transduction efficiencies were observed in many different cell types and target tissues.

The tropism of retroviruses can be altered by introducing foreign envelope proteins and expanding the potential target population of target cells. Lentiviral vectors are retroviral vectors that can transduce or infect non-dividing cells and typically produce high viral titers. Thus, the choice of retroviral gene delivery system will depend on the target tissue. Retroviral vectors are composed of cis-acting long terminal repeats with packaging capacity for foreign sequences of up to 6-10 kb. A minimal cis-acting LTR is sufficient for replication and packaging of the vector, which is then used to integrate the therapeutic gene into target cells to provide permanent transgene expression. Widely used retroviral vectors include those based on murine leukemia virus (MuLV), gibbon simian leukemia virus (GaLV), simian immunodeficiency virus (SIV), human immunodeficiency virus (HIV), and combinations thereof ( See, for example, Buchscher et al., J. Virol. 66:2731-2739 (1992); Johann et al., J. Virol. 66:1635-1640 (1992); :58-59 (1990); Wilson et al., J. Virol. 63:2374-2378 (1989); Miller et al., J. Virol. 65:2220-2224 (1991); reference).

If transient expression is desired, an adenovirus based system may be used. Adenoviral based vectors can have very high transduction efficiencies in many cell types and do not require cell division. Using these vectors, high titers and expression levels were obtained. This vector can be produced in large quantities with a relatively simple system. Adeno-associated virus (“AAV”) vectors can also be used to transduce cells with target nucleic acids, eg, in the in vitro production of nucleic acids and peptides and for in vivo and ex vivo gene therapy procedures (eg, See, for example, West et al., Virology 160:38-47 (1987); U.S. Patent No. 4,797,368; WO 93/24641; Katin, Human Gene Therapy 5:793-801 (1994); Muzyczka, J. Clin. Invest. 94:1351 (1994)). Construction of recombinant AAV vectors is described in U.S. Patent Nos. 5,173,414; See Tratschin et al., Mol. Cell. Biol. 5:3251-3260 (1985); Tratschin, et al., Mol. Cell. Biol. 4:2072-2081 (1984); Hermonat & Muzyczka, PNAS 81:6466-6470 (1984); and Samulski et al., J. Virol. 63:03822-3828 (1989)]. Packaging cells are typically used to form viral particles capable of infecting host cells. Such cells include 293 cells that package adenovirus, and ψJ2 cells or PA317 cells that package retroviruses.

Viral vectors used in gene therapy are usually created by generating cell lines that package nucleic acid vectors into viral particles. Vectors typically contain minimal viral sequences required for packaging and subsequent integration into a host, with other viral sequences replaced by an expression cassette for the polynucleotide(s) to be expressed. Missing viral functions are typically supplied in trans by packaging cell lines. For example, AAV vectors used in gene therapy typically have only the ITR sequences from the AAV genome required for packaging and integration into the host genome. Viral DNA is packaged in cell lines that contain helper plasmids encoding the other AAV genes, rep and cap, but lack ITR sequences.

Cell lines can also be infected with adenovirus as a helper. Helper viruses promote replication of AAV vectors and expression of AAV genes from helper plasmids. Helper plasmids are not packaged in significant quantities due to the lack of ITR sequences. Contamination by adenovirus can be reduced, for example, by heat treatment to which adenovirus is more susceptible than AAV. Additional methods of delivery of nucleic acids to cells are known to those skilled in the art. See, eg, US20030087817, incorporated herein by reference.

In some embodiments, the host cell is transiently or non-transiently transfected with one or more vectors described herein. In some embodiments, the cells are transfected as naturally occurring in the subject. In some embodiments, transfected cells are taken from a subject.

In some embodiments, a transfected cell is a eukaryotic cell. In some embodiments, eukaryotic cells are animal cells (eg, mammals, insects, fish, birds, and reptiles). In some embodiments, the transfected cells are human cells. In some embodiments, the transfected cells are B cells, T cells, natural killer (NK) cells, pluripotent stem cells, induced pluripotent stem cells, chimeric antigen receptor T (CAR-T) cells, monocytes, macrophages and dendritic cells. cells of hematopoietic origin, including but not limited to, such as immune cells (ie, cells of the innate or adaptive immune system).

In some embodiments, the cell is derived from a cell, such as a cell line, taken from a subject. In some embodiments, the cell or cell line is prokaryotic. In some embodiments, the cell or cell line is eukaryotic. In a further embodiment, the cell or cell line is derived from an insect, avian, plant or fungal species. In some embodiments, the cell or cell line may be a mammal, such as, for example, a human, monkey, mouse, cow, pig, goat, hamster, rat, cat, or dog. A wide variety of cell lines for tissue culture are known in the art. Examples of cell lines are C8161, CCRF-CEM, MOLT, mIMCD-3, NHDF, HeLaS3, Huhl, Huh4, Huh7, HUVEC, HASMC, HEKn, HEKa, MiaPaCell, Panel, PC-3, TFl, CTLL-2, CIR, Rat6, CVI, RPTE, AlO, T24, 182, A375, ARH-77, Calul, SW480, SW620, SKOV3, SK-UT, CaCo2, P388Dl, SEM-K2, WEHI-231, HB56, TIB55, lurkat, 145.01, LRMB, Bcl-1, BC-3, IC21, DLD2, Raw264.7, NRK, NRK-52E, MRC5, MEF, Hep G2, HeLa B, HeLa T4, COS, COS-1, COS-6, COS-M6A , BS-C-1 monkey kidney epithelium, BALB/3T3 mouse embryonic fibroblasts, 3T3 Swiss, 3T3-Ll, 132-d5 human fetal fibroblasts; 10.1 mouse fibroblasts, 293-T, 3T3, 721, 9L, A2780, A2780ADR, A2780cis, A172, A20, A253, A431, A-549, ALC, B16, B35, BCP-I cells, BEAS-2B, bEnd. 3, BHK-21, BR 293, BxPC3, C3H-10Tl/2, C6/36, Cal-27, CHO, CHO-7, CHO-IR, CHO-Kl, CHO-K2, CHO-T, CHO Dhfr- /-, COR-L23, COR-L23/CPR, COR-L235010, CORL23/ R23, COS-7, COV-434, CML Tl, CMT, CT26, D17, DH82, DU145, DuCaP, EL4, EM2, EM3, EMT6/AR1, EMT6/AR10.0, FM3, H1299, H69, HB54, HB55, HCA2, HEK-293, HeLa, Hepalclc7, HL-60, HMEC, HT-29, lurkat, lY cells, K562 cells, Ku812, MOR / 0.2R, MONO-MAC 6, MTD-lA, MyEnd, NCI-H69/CPR, NCI-H69/LX10, NCI-H69/LX20, NCI-H69/LX4, NIH-3T3, NALM-1, NW-145 , OPCN/OPCT cell line, Peer, PNT-1A/ PNT 2, RenCa, RIN-5F, RMA/RMAS, Saos-2 cell, Sf-9, SkBr3, T2, T-47D, T84, THPl cell line, U373, U87 , U937, VCaP, Vero cells, WM39, WT-49, X63, YAC-1, YAR, and transgenic variants thereof. Cell lines are available from a variety of sources known to those skilled in the art (see, eg, American Type Culture Collection (ATCC), Manassas, Va.).

In some embodiments, cells transfected with one or more vectors described herein are used to establish new cell lines comprising one or more vector-derived sequences. In some embodiments, using a cell transiently transfected with a fusion protein of the invention and optionally a gRNA, or with a ribonucleoprotein complex of the invention and modified through the activity of the fusion protein or ribonucleoprotein complex, containing a modification However, new cell lines are established that contain cells lacking any other exogenous sequences. In some embodiments, cells transiently or non-transiently transfected with one or more vectors described herein, or cell lines derived from such cells, are used to evaluate one or more test compounds.

In some embodiments, one or more vectors described herein are used to generate non-human transgenic animals or transgenic plants. In some embodiments, a transgenic animal is an insect. In a further embodiment, the insect is an insect pest, such as a mosquito or mite. In some embodiments, the insect is a plant pest, such as corn rootworm or fall armyworm. In some embodiments, the transgenic animal is an avian, such as a chicken, turkey, goose or duck. In some embodiments, the transgenic animal is a mammal, such as a human, mouse, rat, hamster, monkey, ape, rabbit, pig, cow, horse, goat, sheep, cat, or dog.

VI. Variants and fragments of polypeptides and polynucleotides

The present disclosure provides novel adenine deaminase active against DNA molecules, active variants or fragments thereof, and polynucleotides encoding the same, whose amino acid sequences are set forth in SEQ ID NOs: 1-10 and 399-441.

Although the activity of the variant or fragment may be altered relative to the polynucleotide or polypeptide of interest, the variant or fragment should retain the function of the polynucleotide or polypeptide of interest. For example, a variant or fragment may have increased activity, decreased activity, a different spectrum of activity or any other alteration in activity compared to the polynucleotide or polypeptide of interest.

Fragments and variants of the deaminase of the present invention having adenine deaminase activity will retain this activity when they are part of a fusion protein further comprising a DNA-binding polypeptide or fragment thereof.

The term "fragment" refers to a portion of a polynucleotide or polypeptide sequence of the invention. A "fragment" or "biologically active portion" includes a polynucleotide comprising a sufficient number of contiguous nucleotides to retain biological activity (ie, deaminase activity on a nucleic acid). A “fragment” or “biologically active portion” includes a polypeptide comprising a sufficient number of contiguous amino acid residues to retain biological activity. Fragments of the deaminase disclosed herein include shorter than full-length sequences due to the use of alternative downstream start sites. In some embodiments, the biologically active portion of the deaminase is 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, for example, of any of SEQ ID NOs: 1-10 and 399-441. , 110, 120, 130, 140, 150, 160 or more contiguous amino acid residues or variants thereof. Such biologically active moieties can be prepared by recombinant techniques and evaluated for activity.

In general, "variant" is intended to mean substantially similar sequences. For polynucleotides, variants include deletion and/or addition of one or more nucleotides at one or more internal sites within the native polynucleotide and/or substitution of one or more nucleotides at one or more sites within the native polynucleotide. As used herein, a “native” or “wild type” polynucleotide or polypeptide comprises a naturally occurring nucleotide sequence or amino acid sequence, respectively. In the case of polynucleotides, conservative variants include those sequences that encode the native amino acid sequence of the gene of interest because of the degeneracy of the genetic code. Naturally occurring allelic variants such as these can be identified using well-known molecular biology techniques such as the polymerase chain reaction (PCR) and hybridization techniques described below. Variant polynucleotides also include synthetically derived polynucleotides, eg, those created using site-directed mutagenesis but which still encode the polypeptide or polynucleotide of interest. In general, a variant of a particular polynucleotide disclosed herein is at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 55%, at least 60%, as determined by sequence alignment programs and parameters described elsewhere herein. , at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or more sequence identity.

Variants of a particular polynucleotide disclosed herein (i.e., a reference polynucleotide) can also be evaluated by comparison of the percent sequence identity between the polypeptide encoded by the variant polynucleotide and the polypeptide encoded by the reference polynucleotide. Percent sequence identity between any two polypeptides can be calculated using sequence alignment programs and parameters described elsewhere herein. When any given pair of polynucleotides disclosed herein is evaluated by comparison of the percent sequence identity shared by the two polypeptides they encode, the percent sequence identity between the two encoded polypeptides is at least 40%, at least 45%, at least 50% %, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or more sequence identity.

In certain embodiments, a polynucleotide disclosed herein is at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 60% relative to the amino acid sequence of any of SEQ ID NOs: 1-10 and 399-441; At least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89% %, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or more amino acids with identity Encodes an adenine deaminase containing sequence.

Biologically active variants of adenine deaminase of the present invention may contain at least 1-15 amino acid residues, such as at least 1-10, such as at least 6-10, at least 5, at least 4, at least 3, at least 3 may differ by 2 or as few as 1 amino acid residue. In specific embodiments, the polypeptide may comprise a deletion of at least 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60 or more amino acids from the N or C terminus of the polypeptide. N-terminal or C-terminal truncation is included. In some embodiments, the polypeptide is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, internal deletions, which may include deletions of 30, 35, 40, 45, 50, 55, 60 or more amino acids.

It is recognized that modifications can be made to the deaminase provided herein to create variant proteins and polynucleotides. Changes designed by humans can be introduced through the application of site-directed mutagenesis techniques. In some embodiments, natural, as-yet-unknown or as-yet-unidentified polynucleotides and/or polypeptides that are structurally and/or functionally related to the sequences disclosed herein may also be identified as falling within the scope of the present invention. Conservative amino acid substitutions can be made in non-conserved regions that do not alter the function of the polypeptide as an adenine deaminase. In some embodiments, modifications are made to improve the adenine deaminase activity of the deaminase.

Variant polynucleotides and proteins also include sequences and proteins derived from mutagenesis and recombination procedures, such as DNA shuffling. With this procedure, one or more of the different deaminase disclosed herein (eg, SEQ ID NOs: 1-10 and 399-441) are engineered to generate new adenine deaminase with desired properties. In this way, a library of recombinant polynucleotides is generated from a population of related sequence polynucleotides comprising regions of sequences that have substantial sequence identity and are capable of homologous recombination in vitro or in vivo. For example, using this approach, sequence motifs encoding domains of interest can be shuffled between deaminase sequences provided herein and other subsequently identified deaminase genes to obtain improved properties of interest, such as in the case of enzymes. A new gene encoding a protein with an increased K _m can be obtained. Strategies for such DNA shuffling are known in the art. See, eg, Stemmer (1994) Proc. Natl. Acad. Sci. USA 91:10747-10751; Stemmer (1994) Nature 370:389-391; Crameri et al. (1997) Nature Biotech. 15:436-438; Moore et al. (1997) J. Mol. Biol. 272:336-347; Zhang et al. (1997) Proc. Natl. Acad. Sci. USA 94:4504-4509; Crameri et al. (1998) Nature 391:288-291; and US Patent Nos. 5,605,793 and 5,837,458. A "shuffled" nucleic acid is a nucleic acid produced by a shuffling procedure, such as any of the shuffling procedures set forth herein. A shuffled nucleic acid is generated, for example, by (physically or virtually) recombination of two or more nucleic acids (or strings) in an artificial, optionally recursive manner. Generally, one or more screening steps are used in a shuffling process to identify a nucleic acid of interest; This screening step can be performed before or after any recombination step. In some (but not all) shuffling embodiments, it is desirable to perform multiple rounds of recombination prior to selection to increase the diversity of the pools to be screened. The entire process of recombination and selection is optionally repeated recursively. Depending on the context, shuffling can refer to the entire process of recombination and selection, or alternatively it can simply refer to the recombination portion of the overall process.

As used herein, “sequence identity” or “identity” in the context of two polynucleotide or polypeptide sequences refers to residues in the two sequences that are identical when aligned for maximum correspondence over a specified window of comparison. When percentages of sequence identity are used with respect to proteins, residue positions that are not identical often differ by conservative amino acid substitutions, where an amino acid residue is replaced by another amino acid residue with similar chemical properties (e.g., charge or hydrophobicity). , and thus does not alter the functional properties of the molecule. When sequences differ in conservative substitutions, the percent sequence identity can be adjusted upwards to correct for the conservative nature of the substitutions. Sequences that differ by such conservative substitutions are said to have "sequence similarity" or "similarity". Means for such adjustment are well known to those skilled in the art. Typically, this involves increasing the percent sequence identity by scoring conservative substitutions as partial rather than complete mismatches. Thus, for example, if identical amino acids are given a score of 1 and non-conservative substitutions are given a score of 0, conservative substitutions are given a score of 0 to 1. Scoring of conservative substitutions is calculated, for example, as run by the program PC/GENE (Intelligenetics, Mountain View, Calif.).

As used herein, "percentage of sequence identity" means a value determined by comparing two optimally aligned sequences over a window of comparison, wherein the portion of a polynucleotide sequence within the window of comparison is referenced for optimal alignment of the two sequences. It may contain additions or deletions (ie gaps) compared to the sequence (which does not contain additions or deletions). The percentage is calculated by determining the number of positions where the same nucleic acid base or amino acid residue occurs in both sequences to yield the number of matching positions, dividing the number of matching positions by the total number of positions within the comparison window, and multiplying the result by 100 to obtain the sequence sequence. It is calculated by calculating the percentage of identity.

Unless otherwise stated, sequence identity/similarity values provided herein are GAP version 10 using the following parameters; or any equivalent program thereof: % identity and % similarity to a nucleotide sequence, using a GAP weight of 50 and a length weight of 3, and the nwsgapdna.cmp scoring matrix; % identity and % similarity for amino acid sequences using a GAP weight of 8 and a length weight of 2, and the BLOSUM62 scoring matrix. An "equivalent program" is any sequence comparison program that produces an alignment with the same nucleotide or amino acid residue match and the same percent sequence identity when compared to a corresponding alignment generated by GAP version 10 for any two sequences in question. it is intended

Two sequences are "optimally aligned" when they are aligned for similarity scoring using a defined amino acid substitution matrix (e.g., BLOSUM62), gap presence penalty, and gap extension penalty to reach the highest possible score for a pair of sequences. do". Amino acid substitution matrices and their use in quantifying similarity between two sequences are well known in the art and are described, for example, in Dayhoff et al. (1978) "A model of evolutionary change in proteins." In "Atlas of Protein Sequence and Structure," Vol. 5, Suppl. 3 (ed. M. O. Dayhoff), pp. 345-352. Natl. Biomed. Res. Found., Washington, D.C. and Henikoff et al. (1992) Proc. Natl. Acad. Sci. USA 89:10915-10919. The BLOSUM62 matrix is often used as the default scoring substitution matrix in sequence alignment protocols. A gap presence penalty is imposed for the introduction of a single amino acid gap in one of the aligned sequences, and a gap extension penalty is imposed for each additional empty amino acid position inserted into an already opened gap. An alignment is defined by the amino acid positions in each sequence where the alignment begins and ends, optionally by the insertion of a gap or multiple gaps in one or both sequences to reach the highest possible score. Optimal alignment and scoring can be achieved manually, but processes can be achieved using computer-implemented alignment algorithms, such as those described in Altschul et al. (1997) Nucleic Acids Res. 25:3389-3402 and made publicly available on the US National Center for Biological Information website (www.ncbi.nlm.nih.gov). Optimal alignments, including multiple alignments, are available, for example, through www.ncbi.nlm.nih.gov and described in Altschul et al. (1997) Nucleic Acids Res. 25:3389-3402].

With respect to an amino acid sequence optimally aligned to a reference sequence, an amino acid residue "corresponds" to the position in the reference sequence at which the residue is paired in the alignment. A “position” is indicated by a number sequentially identifying each amino acid in the reference sequence based on its position relative to the N-terminus. Due to deletions, insertions, truncations, fusions, etc. that must be taken into account when determining optimal alignment, the number of amino acid residues in a test sequence, usually determined by simply counting from the N-terminus, is equal to the number of its corresponding position in the reference sequence. will not necessarily be identical. For example, if there is a deletion in the aligned test sequence, there will be no amino acid corresponding to a position in the reference sequence at the site of the deletion. If there is an insertion in the aligned reference sequence, that insertion will not correspond to any amino acid position in the reference sequence. In the case of truncation or fusion, there may be a stretch of amino acids in the referenced or aligned sequence that does not correspond to any amino acid in the corresponding sequence.

VII. antibody

A deaminase of the present invention, a fusion protein comprising the deaminase, or a ribonucleoprotein, including those having the amino acid sequence set forth in any one of SEQ ID NOs: 1-10 and 399-441, or active variants or fragments thereof Antibodies are covered. Methods of generating antibodies are well known in the art (see, eg, Harlow and Lane (1988) Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.; and U.S. Patent No. 4,196,265). reference). These antibodies can be used in kits for the detection and isolation of a deaminase described herein or a fusion protein or ribonucleoprotein comprising said deaminase. Thus, the present disclosure specifically relates to a polypeptide or ribonucleoprotein described herein, including, for example, a polypeptide comprising a sequence of at least 85% identity to any of SEQ ID NOs: 1-10 and 399-441. A kit comprising an antibody that binds is provided.

VIII. Systems and ribonucleoprotein complexes for binding to and/or modifying a target sequence of interest and methods for making the same

The present disclosure provides systems for targeting nucleic acid sequences and modifying target nucleic acid sequences. In some embodiments, RNA-guided, DNA-binding polypeptides, such as RGNs, and gRNAs are responsible for targeting the ribonucleoprotein complex to a nucleic acid sequence of interest; The deaminase polypeptide fused to RGDBP is responsible for modifying the targeted nucleic acid sequence so that A>N. In some embodiments, the deaminase converts A>G. The guide RNA directs the RNA-guided, DNA-binding polypeptide to bind to the target sequence by hybridizing to the target sequence of interest and also forming a complex with the RNA-guided, DNA-binding polypeptide. An RNA-guided, DNA-binding polypeptide is one domain of a fusion protein; The second domain is a deaminase described herein. In some embodiments, the RNA-guided, DNA-binding polypeptide is an RGN, such as Cas9. Other examples of RNA-guided, DNA-binding polypeptides include RGNs, such as those described in International Patent Application Publication Nos. WO 2019/236566 and WO 2020/139783. In some embodiments, the RNA-guided, DNA-binding polypeptide is a type II CRISPR-Cas polypeptide, or an active variant or fragment thereof. In some embodiments, the RNA-guided, DNA-binding polypeptide is a Type V CRISPR-Cas polypeptide, or an active variant or fragment thereof. In some embodiments, the RNA-guided, DNA-binding polypeptide is a Type VI CRISPR-Cas polypeptide. In some embodiments, the DNA-binding domain of the fusion protein does not require an RNA guide, such as a zinc finger nuclease, TALEN or meganuclease polypeptide. In some embodiments, the nuclease activity of the DNA-binding domain is partially or completely inactivated. In a further embodiment, the RNA-guided, DNA-binding polypeptide is an RGN, such as for example APG07433.1 (SEQ ID NO: 41), or an active variant or fragment thereof, such as the nickase nAPG07433.1 (SEQ ID NO: 41). 42) or other nickase RGN variants described in the Examples (SEQ ID NOs: 52-59, 61, 397, and 398).

In some embodiments, a system for binding to and modifying a target sequence of interest provided herein is a ribonucleoprotein complex, which is at least one molecule of RNA bound to at least one protein. A ribonucleoprotein complex provided herein comprises at least one guide RNA as an RNA component, and a fusion protein comprising a deaminase of the invention and an RNA-guided, DNA-binding polypeptide as a protein component. In some embodiments, the ribonucleoprotein complex is purified from a cell or organism transformed with a polynucleotide encoding the fusion protein and guide RNA and cultured under conditions permissive for expression of the fusion protein and guide RNA.

In various embodiments, a ribonucleoprotein complex comprising any of the fusion proteins described herein and a guide RNA linked to a DNA-binding polypeptide of the fusion protein is provided. For example, provided herein is a ribonucleoprotein complex comprising a fusion protein with a deaminase comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO:407. In another example, a ribonucleoprotein complex comprising a fusion protein with a deaminase comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 399 is provided. In another example, a ribonucleoprotein complex comprising a fusion protein with a deaminase comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 405 is provided. In some embodiments of the ribonucleoprotein complex described above, the fusion protein is CasX, CasY, C2c1, C2c2, C2c3, GeoCas9, aSpCas9, SaCas9, Nme2Cas9, CjCas9, Cas12a (previously known as Cpf1), Cas12b, Cas12g, Cas12h , Cas12i, LbCas12a, AsCas12a, CasMINI, Cas13b, Cas13c, Cas13d, Cas14, Csn2, xCas9, SpCas9-NG, LbCas12a, AsCas12a, Cas9-KKH, circular permutation Cas9, Argonauts (Ago), SmacCas9, Spy-macCas9 domain, or an RGN selected from RGNs having an amino acid sequence set forth in any one of SEQ ID NOs: 41, 60, 366, or 368. In some embodiments, the ribonucleoprotein complex comprises SEQ ID NOs: 42, 52-59, 61, 397 and SEQ ID NOs: 42, 52-59, 61, 397 and fused to a deaminase comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 407. 398 with an amino acid sequence having at least 95% sequence identity to any one of the nickases. In some embodiments, the ribonucleoprotein complex comprises SEQ ID NOs: 42, 52-59, 61, 397 and SEQ ID NOs: 42, 52-59, 61, 397 and fused to a deaminase comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 399. 398 with an amino acid sequence having at least 95% sequence identity to any one of the nickases. In some embodiments, the ribonucleoprotein complex comprises SEQ ID NOs: 42, 52-59, 61, 397 and SEQ ID NOs: 42, 52-59, 61, 397 and fused to a deaminase comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 405. 398 with an amino acid sequence having at least 95% sequence identity to any one of the nickases. In some embodiments, the ribonucleoprotein complex comprises a Cas9 nickase fused to a deaminase comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO:407. In some embodiments, the ribonucleoprotein complex comprises a Cas9 nickase fused to a deaminase comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO:399. In some embodiments, the ribonucleoprotein complex comprises a Cas9 nickase fused to a deaminase comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO:405. The Cas9 nickase can be any Cas9 nickase disclosed in PCT Patent Publication No. WO2020181195, the entire contents of which are incorporated herein by reference. In various embodiments described herein, the ribonucleoprotein complex may also contain a gRNA described herein.

A method for preparing a deaminase, fusion protein or fusion protein ribonucleoprotein complex is provided. Such methods include culturing cells comprising a nucleotide sequence encoding a deaminase, a fusion protein, and in some embodiments a guide RNA under conditions in which the deaminase or fusion protein (and in some embodiments, the guide RNA) is expressed. include that The deaminase, fusion protein or fusion ribonucleoprotein can then be purified from the lysate of the cultured cells.

Methods for purifying deaminase, fusion proteins or fusion ribonucleoprotein complexes from lysates of biological samples are known in the art (e.g., size exclusion and/or affinity chromatography, 2D-PAGE, HPLC , reverse phase chromatography, immunoprecipitation). In a particular method, the deaminase or fusion protein is produced recombinantly and includes glutathione-S-transferase (GST), chitin binding protein (CBP), maltose binding protein, thioredoxin (TRX), poly(NANP) , tandem affinity purification (TAP) tag, myc, AcV5, AU1, AU5, E, ECS, E2, FLAG, HA, nus, Softtag 1, Softtag 3, Strep, SBP, Glu-Glu, HSV, KT3, S, S1, T7, V5, VSV-G, 6xHis, biotin carboxyl carrier protein (BCCP), and purification tags to assist in their purification, including but not limited to, calmodulin. Generally, the tagged deaminase, fusion protein or fusion ribonucleoprotein complex is purified using immunoprecipitation or other similar methods known in the art.

An "isolated" or "purified" polypeptide, or biologically active portion thereof, is substantially or essentially free of components that normally accompany or interact with the polypeptide found in its naturally occurring environment. Thus, an isolated or purified polypeptide is substantially free of other cellular material, or culture medium when produced by recombinant techniques, or substantially free of chemical precursors or other chemicals when chemically synthesized. Proteins that are substantially free of cellular material include protein preparations having less than 30%, less than 20%, less than 10%, less than 5%, or less than 1% (by dry weight) of contaminating proteins. When a protein of the invention or a biologically active portion thereof is produced recombinantly, an optimal culture medium contains less than 30%, less than 20%, less than 10%, less than 5%, or less than 1% (by dry weight) of chemical precursors or Indicates a non-interesting protein chemical.

Certain methods provided herein for binding and/or cleaving a target sequence of interest involve the use of a ribonucleoprotein complex. In some embodiments, ribonucleoprotein complexes are assembled in vitro. In vitro assembly of a ribonucleoprotein complex can be performed by any method known in the art in which an RGDBP polypeptide or fusion protein comprising the same is contacted with a guide RNA under conditions such that the RGDBP polypeptide or fusion protein comprising the same binds to the guide RNA. can be performed using As used herein, "contacting", "contacting", "contacted" refers to bringing together the components of a desired reaction under conditions suitable for carrying out the desired reaction. In some embodiments of the described methods of modifying a target DNA molecule, the contacting step is performed in vitro. In some embodiments, the contacting step is performed in vivo. In some embodiments, the contacting step is performed on a subject (eg, a human subject or a non-human animal subject). In some embodiments, the contacting step is performed on a cell, such as a human or non-human animal cell. The RGDBP polypeptide or fusion protein comprising it may be purified from a biological sample, cell lysate, or culture medium, produced through in vitro translation, or chemically synthesized. Guide RNAs can be purified from biological samples, cell lysates, or culture media, transcribed in vitro, or chemically synthesized. The RGDBP polypeptide or fusion protein comprising the same and guide RNA can be contacted in solution (eg, buffered saline solution) to allow in vitro assembly of ribonucleoprotein complexes.

IX. Methods for Modifying the Target Sequence

The present disclosure provides methods for modifying a target nucleic acid molecule of interest (eg, a target DNA molecule). The method comprises delivering a fusion protein comprising a DNA-binding polypeptide and at least one deaminase of the invention or a polynucleotide encoding the same to a target sequence or a cell, organelle or embryo comprising the target sequence. In certain embodiments, the method comprises at least one guide RNA or polynucleotide encoding the same, and at least one deaminase of the invention and at least one RNA-guided, DNA-binding polypeptide or polynucleotide encoding the same. It includes delivering a system comprising a fusion protein of to a target sequence or a cell, organelle or embryo comprising the target sequence. In some embodiments, the fusion protein comprises any one of the amino acid sequences of SEQ ID NOs: 1-10 and 399-441, or an active variant or fragment thereof.

In some embodiments, the method comprises combining a DNA molecule with (a) a deaminase and an RNA-guided, DNA-binding polypeptide, such as a fusion protein comprising, for example, a nuclease-inactive or nickase Cas9 domain; and (b) contacting the fusion protein of (a) with a gRNA that targets a target nucleotide sequence of a DNA molecule; wherein the DNA molecule is contacted with the fusion protein and gRNA under conditions suitable for deamination of nucleobases and in an effective amount. In some embodiments, the target DNA molecule comprises a sequence associated with a disease or disorder, wherein deamination of a nucleobase results in a sequence not associated with the disease or disorder. In some embodiments, the disease or disorder affects an animal. In a further embodiment, the disease or disorder affects a mammal, such as a human, cow, horse, dog, cat, goat, sheep, pig, monkey, rat, mouse or hamster. In some embodiments, the target DNA sequence is present in an allele of a crop plant, wherein a particular allele with a trait of interest produces a plant with less agronomic value. Deamination of nucleobases creates alleles that improve traits and increase the agronomic value of plants.

In embodiments where the method comprises delivering a polynucleotide encoding a guide RNA and/or fusion protein, the cell or embryo can then be cultured under conditions in which the guide RNA and/or fusion protein are expressed. In various embodiments, the method comprises contacting a target sequence with a ribonucleoprotein complex comprising a gRNA and a fusion protein comprising a deaminase and an RNA-guided DNA-binding polypeptide of the invention. In certain embodiments, a method comprises introducing a ribonucleoprotein complex of the invention into a cell, organelle, or embryo comprising a target sequence. The ribonucleoprotein complexes of the present invention may be purified from a biological sample, recombinantly produced and subsequently purified, or in vitro-assembled, as described herein. In embodiments in which a ribonucleoprotein complex contacted with a target sequence or organelle or embryo is assembled in vitro, the method may further include in vitro assembly of the complex prior to contact with the target sequence, cell, organelle, or embryo. .

Purified or in vitro assembled ribonucleoprotein complexes of the present invention can be introduced into cells, organelles, or embryos using any method known in the art, including but not limited to electroporation. In some embodiments, fusion proteins comprising a deaminase and an RNA-guided, DNA-binding polypeptide of the invention, and a polynucleotide encoding or comprising a guide RNA are prepared by any method known in the art (eg eg, electroporation) into cells, organelles, or embryos.

Upon delivery to or contact with the target sequence, or a cell, organelle, or embryo comprising the target sequence, the guide RNA directs the fusion protein to bind the target sequence in a sequence-specific manner. The target sequence can subsequently be modified via the deaminase domain of the fusion protein. In some embodiments, binding of such fusion proteins to a target sequence results in modification of nucleotides adjacent to the target sequence. Nucleobases adjacent to the target sequence modified by deaminase are 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 base pairs . A fusion protein comprising a deaminase and an RNA-guided, DNA-binding polypeptide of the present invention is capable of introducing a targeted A>N, preferably a targeted A>G mutation into a targeted DNA molecule.

In some embodiments of the described methods of modifying a target DNA molecule, the contacting step is performed in vitro. In certain embodiments, the contacting step is performed in vivo. In some embodiments, the contacting step is performed on a subject (eg, a human subject or a non-human animal subject). In some embodiments, the contacting step is performed on a cell, such as a human or non-human animal cell.

Methods for measuring binding of a fusion protein to a target sequence are known in the art and include chromatin immunoprecipitation assays, gel mobility shift assays, DNA pull-down assays, reporter assays, microplate capture and detection assays. Likewise, methods for measuring cleavage or modification of a target sequence are known in the art and include attachment of an appropriate label (eg, radioisotope, fluorescent material) to the target sequence to facilitate detection of degradation products. In vitro or in vivo cleavage assays in which cleavage is confirmed using PCR, sequencing, or gel electrophoresis, in the presence or absence of. In some embodiments, a nicking trigger exponential amplification reaction (NTEXPAR) assay is used (see, eg, Zhang et al. (2016) Chem. Sci. 7:4951-4957). In vivo cleavage can be assessed using the Surveyor assay (Guschin et al. (2010) Methods Mol Biol 649:247-256).

In some embodiments, the method involves the use of an RNA-binding, DNA-guided domain as part of a fusion protein complexed with more than one guide RNA. More than one guide RNA may target different regions of a single gene or may target multiple genes. This multiple targeting allows the deaminase domain of the fusion protein to modify the nucleic acid, thereby introducing multiple mutations into the target nucleic acid molecule of interest (eg, genome).

The method is directed to single-stranded RNA-guided nucleases (RGNs), such as nickase RGNs (i.e., double-stranded polynucleotides, eg, nAPG07433.1 (SEQ ID NOs: 42 or SEQ ID NOs: 50-57)). can cleave only), the method may include introducing two different RGNs or RGN variants that target the same or overlapping target sequences and cleave different strands of the polynucleotide. For example, an RGN nickase that cleave only the positive (+) strand of the double-stranded polynucleotide can be introduced together with a second RGN nickase that cleave only the negative (-) strand of the double-stranded polynucleotide. In some embodiments, two different fusion proteins are provided, wherein each fusion protein comprises a different RGN with a different PAM recognition sequence, so that a greater diversity of nucleotide sequences can be targeted for mutation.

One skilled in the art will appreciate that targeting a single target sequence or multiple target sequences can be achieved using any of the methods disclosed herein. Thus, methods include the use of fusion proteins comprising a single RNA-guided, DNA-binding polypeptide in combination with multiple distinct guide RNAs capable of targeting a single gene and/or multiple distinct sequences within multiple genes. do. The deaminase domain of the fusion protein will then introduce mutations into each targeted sequence. Also encompassed herein are methods wherein multiple separate guide RNAs are introduced in combination with multiple separate RNA-guided, DNA binding polypeptides. Such RNA-guided, DNA-binding polypeptides may be multiple RGNs or RGN variants. These guide RNA and guide RNA/fusion protein systems can target a single gene and/or multiple distinct sequences within multiple genes.

In some embodiments, a fusion protein comprising an RNA-guided, DNA-binding polypeptide and a deaminase polypeptide of the invention can be used to create a mutation in a targeted gene or targeted region of a gene of interest. In some embodiments, the fusion proteins of the invention can be used for saturation mutagenesis of a target gene or target region of a gene of interest, followed by high-throughput forward genetic screening to identify novel mutations and/or phenotypes. In some embodiments, the fusion proteins described herein can be used to create mutations at targeted genomic locations that may or may not include a coding DNA sequence. Libraries of cell lines generated by the targeted mutagenesis described above may also be useful for the study of gene function or gene expression.

X. Target Polynucleotide

In one aspect, the invention provides a method of modifying a target polynucleotide in a eukaryotic cell, which may be in vivo, ex vivo or in vitro. In some embodiments, the method comprises sampling a cell or cell population from a human or non-human animal or plant (including microalgae) and modifying the cell or cells. Culturing can occur at any ex vivo stage. The cell or cells can even be reintroduced into humans, non-human animals or plants (including microalgae).

Using natural variability, plant breeders combine the most useful genes for desirable qualities such as yield, quality, uniformity, firmness, and resistance to pests. These desirable qualities may also include growth, photoperiod preference, temperature requirements, initiation date of floral or reproductive development, fatty acid content, insect resistance, disease resistance, nematode resistance, fungal resistance, herbicide resistance, various environmental factors such as drought, heat, moisture, It includes tolerance to adverse soil conditions including cold, wind, and high salinity. Sources of these useful genes include natural or exotic varieties, native varieties, wild plant congeners, and induced mutations, eg, treatment of plant material with mutagens. Using the present invention, plant breeders are provided with a new tool for inducing mutations. Thus, one skilled in the art can use the present invention to induce elevation of useful genes with greater precision than previous mutagens, thereby accelerating and improving plant breeding programs.

The target polynucleotide of the deaminase or fusion protein of the present invention can be any polynucleotide endogenous or exogenous to the eukaryotic cell. For example, a target polynucleotide can be a polynucleotide present in the nucleus of a eukaryotic cell. In some embodiments, a target polynucleotide is a sequence encoding a gene product (eg, a protein) or a non-coding sequence (eg, a regulatory polynucleotide or junk DNA). In some embodiments, a target sequence for a fusion protein of the invention is a PAM (protospacer adjacent motif); that is, it associates with a short sequence recognized by an RNA-guided DNA-binding polypeptide. The exact sequence and length requirements for PAMs vary depending on the RNA-guided DNA-binding polypeptide used, but PAMs are typically sequences of 2-5 base pairs adjacent to a protospacer (ie, the target sequence).

The target polynucleotides of the fusion proteins of the present invention may include multiple disease-associated genes and polynucleotides as well as signaling biochemical pathway-associated genes and polynucleotides. Examples of target polynucleotides include sequences associated with signaling biochemical pathways, eg, signaling biochemical pathway-associated genes or polynucleotides. Examples of target polynucleotides include disease-associated genes or polynucleotides. A "disease-associated" gene or polynucleotide is any gene or polynucleotide that produces a transcription or translation product at an abnormal level or in an abnormal form in a cell derived from a disease-diseased tissue compared to a tissue or cell from a non-disease control. refers to It can be a gene that is expressed at an abnormally high level; It can be a gene that is expressed at abnormally low levels, where altered expression correlates with development and/or progression of a disease. A disease-associated gene also refers to a gene that has mutation(s) or genetic variation (eg, a causal mutation) that is directly responsible for, or is in linkage disequilibrium with, the gene(s) responsible for the pathogenesis of a disease. Transcription or translation products may be known or unknown, and may further be at normal or abnormal levels.

Non-limiting examples of disease-associated genes that can be targeted using the methods and compositions disclosed herein are provided in Table 34. In some embodiments, targeted disease-associated genes are those disclosed in Table 34 with a G>A mutation. Additional examples of disease-associated genes and polynucleotides are available on the World Wide Web from the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Maryland. Baltimore) and the National Center for Biological Information, National Library of Medicine (Bethesda, MD).

In some embodiments, the target polynucleotide comprises a cystic fibrosis transmembrane conductance regulator (5) gene.

As used herein, the term “cystic fibrosis transmembrane conductance regulator” or “CFTR” refers to a cAMP regulated chloride channel located in the apical membrane of epithelial cells that catalyzes the passage of small ions across the membrane. A non-limiting example of a CFTR gene is presented as SEQ ID NO:51.

The term "targets" or "targets," as used herein with reference to spacer sequences and target sequences, refers to the ability of an RNA-guided nuclease to sufficiently hybridize to a target sequence, based on the ability of the spacer sequence within the associated guide RNA to sufficiently hybridize. refers to being localized in

A CRISPR RNA (crRNA) or nucleic acid molecule encoding it is provided, wherein the crRNA comprises a spacer sequence that targets a CFTR target sequence. A guide RNA comprising such a crRNA, one or more nucleic acid molecules encoding a guide RNA comprising such a crRNA, a vector comprising one or more nucleic acid molecules encoding a guide RNA comprising such a crRNA, and a system comprising such a crRNA Also provided. Such a crRNA or a nucleic acid molecule encoding it, a guide RNA comprising such a crRNA, one or more nucleic acid molecules encoding a guide RNA comprising such a crRNA, a vector comprising one or more nucleic acid molecules encoding a guide RNA comprising such a crRNA , and methods of binding, cleavage, and/or modulating target sequences using systems comprising such crRNAs are also provided.

In some embodiments, the CFTR target sequence of the crRNA or guide RNA is set forth in any one of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364, 562 and 563 sequence or its complement. In some embodiments, a single guide RNA (sgRNA) comprising a crRNA with a spacer sequence targeting a CFTR target sequence is SEQ ID NO: 98-115, 140-151, 186-202, 235-250, 287-304; at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92% for any of 345-364 and 564; 93%, 94%, 95%, 96%, 97%, 98%, 99% or greater sequence identity.

In some embodiments, the CFTR target sequence of the crRNA or guide RNA is SEQ ID NOs: 62-68, 80-85, 116-119, 128-131, 163, 164, 180, 181, 203-209, 219-225, 256-258, 274-276, 310-313, and 330-333, or the complement thereof, wherein the associated RGN polypeptide is at least 40%, 45%, 50% relative to SEQ ID NO: 53 , 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99 has an amino acid sequence with % or greater sequence identity. In some embodiments, an sgRNA comprising a crRNA having a spacer sequence targeting a CFTR target sequence is one of SEQ ID NOs: 98-104, 140-143, 197, 198, 235-241, 292-294, and 350-353 at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, have 95%, 96%, 97%, 98%, 99% or greater sequence identity, and the associated RGN polypeptide has at least 40%, 45%, 50%, 55%, 60% to SEQ ID NO:53 , 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more sequences have identical amino acid sequences.

In some embodiments, the CFTR target sequence of the crRNA or guide RNA is SEQ ID NOs: 68-71, 86-89, 120-122, 132-134, 152-156, 169-173, 213-215, 229-231, 251-255, 269-273, 305-309 and 325-329, or the complement thereof, wherein the associated RGN polypeptide is at least 40%, 45%, 50% relative to SEQ ID NO: 55; 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or an amino acid sequence with greater sequence identity. In some embodiments, an sgRNA comprising a crRNA having a spacer sequence targeting a CFTR target sequence is one of SEQ ID NOs: 104-107, 144-146, 186-190, 245-247, 287-291, and 345-349 at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, have 95%, 96%, 97%, 98%, 99% or greater sequence identity, and the associated RGN polypeptide has at least 40%, 45%, 50%, 55%, 60% to SEQ ID NO:55 , 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more sequences have identical amino acid sequences.

In some embodiments, the CFTR target sequence of the crRNA or guide RNA is a sequence set forth in any one of SEQ ID NOs: 72, 73, 90, 91, 161, 162, 178, 179, 265, 266, 283, and 284, or the complement thereof. The sieve and associated RGN polypeptides are at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, and has an amino acid sequence that has 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or greater sequence identity. In some embodiments, an sgRNA comprising a crRNA having a spacer sequence targeting a CFTR target sequence is at least 40%, 45%, 50% relative to any one of SEQ ID NOs: 108, 109, 195, 196, 301 and 302 , 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99 % or greater sequence identity, and the associated RGN polypeptides have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, has an amino acid sequence that has 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or greater sequence identity.

In some embodiments, the CFTR target sequence of the crRNA or guide RNA is SEQ ID NO: 74, 75, 92, 93, 123, 124, 135, 136, 167, 184, 216-218, 232-234, 259-261, 277-279, 314-317, and 334-337, or the complement thereof, wherein the associated RGN polypeptide is at least 40%, 45%, 50%, 55% relative to SEQ ID NO: 56 , 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more It has an amino acid sequence that has more than one sequence identity. In some embodiments, the sgRNA comprising a crRNA with a spacer sequence targeting a CFTR target sequence is to any one of SEQ ID NOs: 110, 111, 147, 148, 201, 248-250, 295-297 and 354-357 at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, have 96%, 97%, 98%, 99% or greater sequence identity, and the associated RGN polypeptide has at least 40%, 45%, 50%, 55%, 60%, 65% to SEQ ID NO: 56 , 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more sequence identity. has an amino acid sequence.

In some embodiments, the CFTR target sequence of the crRNA or guide RNA has a sequence set forth in any one of SEQ ID NOs: 76, 94, 210-212, 226-228, 322, 342, 562 and 563, or the complement thereof; The associated RGN polypeptide is at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92 relative to SEQ ID NO: 42 %, 93%, 94%, 95%, 96%, 97%, 98%, 99% or greater sequence identity. In some embodiments, an sgRNA comprising a crRNA with a spacer sequence targeting a CFTR target sequence is at least 40%, 45%, 50%, 55% relative to any one of SEQ ID NOs: 112, 242-244, 362 and 564 %, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or RGN polypeptides associated with sequence identity greater than that have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85% to SEQ ID NO:42 , 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more sequence identity.

In some embodiments, the CFTR target sequence of the crRNA or guide RNA has a sequence set forth in any one of SEQ ID NOs: 77, 95, 125, 137, 157-160, 174-177, 323 and 343, or the complement thereof; The associated RGN polypeptide is at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92% relative to SEQ ID NO: 54 %, 93%, 94%, 95%, 96%, 97%, 98%, 99% or greater sequence identity. In some embodiments, an sgRNA comprising a crRNA with a spacer sequence targeting a CFTR target sequence is at least 40%, 45%, 50%, 55% relative to any one of SEQ ID NOs: 113, 149, 191-194, and 363 %, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or have greater than that sequence identity, and the associated RGN polypeptide has at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85% to SEQ ID NO: 54 , 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more sequence identity.

In some embodiments, the CFTR target sequence of the crRNA or guide RNA is a sequence set forth in any one of SEQ ID NOs: 78, 96, 126, 138, 168, 185, 267, 285, 318, 319, 338 and 339, or the complement thereof. The sieve and associated RGN polypeptides have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, and has an amino acid sequence that has 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or greater sequence identity. In some embodiments, an sgRNA comprising a crRNA with a spacer sequence targeting a CFTR target sequence is at least 40%, 45%, 50% relative to any one of SEQ ID NOs: 114, 150, 202, 303, 358 and 359 , 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99 % or greater sequence identity, and the associated RGN polypeptides have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, has an amino acid sequence that has 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or greater sequence identity.

In some embodiments, the CFTR target sequence of the crRNA or guide RNA has a sequence set forth in any one of SEQ ID NOs: 79, 97, 127, 139, 262-264, 280-282, 324 and 344, or the complement thereof; The associated RGN polypeptide is at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92% relative to SEQ ID NO: 58 %, 93%, 94%, 95%, 96%, 97%, 98%, 99% or greater sequence identity. In some embodiments, an sgRNA comprising a crRNA with a spacer sequence targeting a CFTR target sequence is at least 40%, 45%, 50%, 55% relative to any one of SEQ ID NOs: 115, 151, 298-300 and 364 %, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or and the associated RGN polypeptide has at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85% to SEQ ID NO: 58. , 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more sequence identity.

In some embodiments, the CFTR target sequence of the crRNA or guide RNA has a sequence set forth in any one of SEQ ID NOs: 165, 166, 182, 183, 268, 286, 320, 321, 340 and 341, or the complement thereof; The associated RGN polypeptide is at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92% relative to SEQ ID NO: 59 %, 93%, 94%, 95%, 96%, 97%, 98%, 99% or greater sequence identity. In some embodiments, an sgRNA comprising a crRNA with a spacer sequence targeting a CFTR target sequence is at least 40%, 45%, 50%, 55% relative to any one of SEQ ID NOs: 199, 200, 304, 360 and 361 %, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or RGN polypeptides that have greater sequence identity and are associated with at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85% to SEQ ID NO: 59 , 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more sequence identity.

In some embodiments, the method comprises contacting a DNA molecule comprising a target DNA sequence with a DNA-binding polypeptide-deaminase fusion protein of the invention, wherein the DNA molecule is subjected to conditions suitable for deamination of a nucleobase. and with the fusion protein in an effective amount. In certain embodiments, the method comprises binding a DNA molecule comprising a target DNA sequence to (a) an RGN-deaminase fusion protein of the invention; and (b) contacting the fusion protein of (a) with a gRNA that targets the target nucleotide sequence of the DNA strand; wherein the DNA molecule is contacted with the fusion protein and gRNA under conditions suitable for deamination of nucleobases and in an effective amount. In some embodiments, the target DNA sequence comprises a sequence associated with a disease or disorder, wherein deamination of a nucleobase results in a sequence not associated with the disease or disorder. In some embodiments, the target DNA sequence is present in an allele of a crop plant, wherein a particular allele with a trait of interest produces a plant with less agronomic value. Deamination of nucleobases creates alleles that improve traits and increase the agronomic value of plants.

In some embodiments, the target DNA sequence comprises a G>A point mutation associated with a disease or disorder, wherein deamination of the mutant A base results in a sequence not associated with the disease or disorder. In some embodiments, deamination corrects point mutations in sequences associated with a disease or disorder.

In some embodiments, the sequence associated with the disease or disorder encodes a protein, and the deamination introduces a stop codon into the sequence associated with the disease or disorder, resulting in truncation of the encoded protein. In some embodiments, contacting is performed in vivo in a subject predisposed to, having, or diagnosed with a disease or disorder. In some embodiments, the disease or disorder is a disease associated with a point mutation or single-base mutation in a genome. In some embodiments, the disease is a genetic disease, cancer, metabolic disease, or lysosomal storage disease.

XI. Pharmaceutical compositions and methods of treatment

Provided herein are methods of treating a disease in a subject in need thereof. The method comprises administering to a subject in need thereof an effective amount of a fusion protein disclosed herein or a polynucleotide encoding the same, a gRNA disclosed herein or a polynucleotide encoding the same, a fusion protein system disclosed herein, a ribonucleoprotein complex disclosed herein, or any of these and administering cells modified by or comprising any one of the compositions.

In some embodiments, the treatment comprises in vivo gene editing by administering to a subject in need thereof a fusion protein, gRNA, or fusion protein system disclosed herein, or polynucleotide(s) encoding the same, to a subject in need thereof. In some embodiments, treatment comprises ex vivo gene editing, wherein a cell is genetically modified ex vivo with a fusion protein, gRNA, or fusion protein system disclosed herein, or polynucleotide(s) encoding the same, followed by ex vivo gene editing. The modified cells are administered to a subject. In some embodiments, genetically modified cells originate from a subject, then the modified cells are administered, and the transplanted cells are referred to herein as autologous. In some embodiments, the genetically modified cells are from a different subject (ie, donor) within the same species as the subject to which the modified cells are administered (ie, recipient), and the transplanted cells are referred to herein as allogeneic. In some examples described herein, cells may be expanded in culture prior to administration to a subject in need thereof.

For example, in some embodiments, a subject having a genetic defect associated with the disease, eg, the CFTR gene, is provided with an amino acid sequence that is at least 80% identical to the sequence set forth in any one of SEQ ID NOs: 399 and 405-407. A method comprising administering an effective amount of a ribonucleoprotein complex comprising a fusion protein with a deaminase having In embodiments described herein, administration of the ribonucleoprotein complex corrects a point mutation or introduces a deactivating mutation into the disease-associated CFTR gene. Other diseases that can be treated by correcting point mutations or introducing deactivating mutations into disease-associated genes will be known to those skilled in the art, and the present disclosure is not limited in this respect.

In some embodiments, a disease to be treated with a composition disclosed herein is one that can be treated with immunotherapy, such as chimeric antigen receptor (CAR) T cells. Such diseases include, but are not limited to, cancer.

In some embodiments, deamination of the target nucleobase results in the correction of a genetic defect, for example to correct the CFTR gene, or the correction of a point mutation leading to loss of function in a gene product. In some embodiments, the genetic defect is associated with a disease or disorder, eg, a lysosomal storage disorder or a metabolic disease, such as, eg, type I diabetes. Thus, in some embodiments, a disease to be treated with a composition disclosed herein is a sequence that is mutated to treat the disease or disorder or reduce symptoms associated with the disease or disorder (i.e., the sequence is causal for the disease or disorder, or the disease or disorder cause for the symptoms associated with the disorder).

In some embodiments, the disease to be treated with a composition disclosed herein is associated with a causal mutation. As used herein, "causative mutation" refers to a particular nucleotide, nucleotides, or nucleotide sequence in a genome that contributes to the severity or presence of a disease or disorder in a subject. Correction of the causal mutation leads to improvement of at least one symptom resulting from the disease or disorder. In some embodiments, correction of the causal mutation results in improvement of at least one symptom resulting from the disease or disorder. In some embodiments, the causative mutation is adjacent to a PAM site recognized by RGDBP (eg, RGN) fused to a deaminase disclosed herein. A causal mutation can be corrected with a fusion polypeptide comprising RGDBP (eg, RGN) and a deaminase disclosed herein. Non-limiting examples of diseases associated with causal mutations include cystic fibrosis, Hurler syndrome, Friedreich's ataxia, Huntington's disease and sickle cell disease. Additional non-limiting examples of disease-associated genes and mutations are available on the World Wide Web from the McCusick-Natans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD) and the National Center for Biological Information, National Library of Medicine (Bethesda, MD). is available from

In some embodiments, the methods provided herein are used to introduce a deactivating point mutation into a gene or allele encoding a gene product associated with a disease or disorder. For example, in some embodiments, provided herein are methods of using fusion proteins to introduce inactivating point mutations into oncogenes (eg, in the treatment of proliferative diseases). Deactivating mutations, in some embodiments, can create a premature stop codon in the coding sequence, which results in the expression of a truncated gene product, eg, a truncated protein that lacks the function of a full-length protein. In some embodiments, the purpose of the methods provided herein is to restore function of a dysfunctional gene through genome editing. Fusion proteins provided herein can be validated for gene editing-based human therapeutics in vitro, for example, by correcting disease-associated mutations in human cell culture. It is common in the art that fusion proteins provided herein, e.g., fusion proteins comprising an RNA-guided, DNA-binding polypeptide and a deaminase polypeptide, can be used to correct any single point G>A mutation. will be understood by the technicians of Deamination of mutant A to G leads to correction of the mutation.

As used herein, “treatment” or “treating” or “mitigating” or “improving” are used interchangeably. These terms refer to an approach for obtaining beneficial or desired results, including but not limited to therapeutic benefit and/or prophylactic benefit. By therapeutic benefit is meant any therapeutically appropriate improvement in or effect on one or more diseases, conditions or symptoms under treatment. For prophylactic benefit, the composition may be administered to a subject at risk of developing a particular disease, condition or symptom, or to a subject reporting one or more of the physiological symptoms of a disease, even though the disease, condition or symptom may not yet appear. there is. In some embodiments, treatment may be administered after one or more symptoms have developed and/or after the disease has been diagnosed. In certain embodiments, treatment may be administered in the absence of symptoms, for example to prevent or delay the onset of symptoms or to inhibit the onset or progression of a disease. For example, treatment can be administered to a susceptible individual prior to the onset of symptoms (eg, in light of a history of symptoms and/or in light of genetic or other susceptibility factors). Treatment may also be continued after the symptoms have resolved, eg to prevent or delay their recurrence.

The term "effective amount" or "therapeutically effective amount" refers to an amount of an agent sufficient to achieve a beneficial or desired result. A therapeutically effective amount may vary depending on one or more of the subject and disease state to be treated, the weight and age of the subject, the severity of the disease state, the mode of administration, and the like, and can be readily determined by those skilled in the art. The specific dosage may vary depending on one or more of the particular agent selected, the dosage regimen to be followed, whether or not it is administered in combination with other compounds, the timing of administration, and the delivery system to be implemented.

The term "administering" refers to placing the active ingredient into a subject by a method or route that at least partially localizes the introduced active ingredient to the desired site, such as the site of damage or repair, so as to produce the desired effect(s). . In some embodiments, the present disclosure provides methods comprising delivering any of the isolated polypeptides, nucleic acid molecule fusion proteins, ribonucleoprotein complexes, vectors, pharmaceutical compositions, and/or gRNAs described herein. In some embodiments, the disclosure further provides cells produced by such methods, and organisms (eg, animals or plants) comprising or produced from such cells. In some embodiments, a deaminase, fusion protein, and/or nucleic acid molecule as described herein combined with (and optionally complexed with) a guide sequence is delivered to a cell.

In some embodiments, administration comprises administration by viral delivery. A viral vector comprising a nucleic acid encoding a fusion protein, ribonucleoprotein complex or vector disclosed herein can be administered directly to a patient (i.e., in vivo) or used to treat cells in vitro, and can be modified The cells may optionally be administered to a patient (ie, ex vivo). Conventional viral based systems may include, but are not limited to, retroviral, lentiviral, adenoviral, adeno-associated and herpes simplex virus vectors for gene delivery. Integration in the host genome is possible by retroviral, lentiviral, and adeno-associated viral gene transfer methods, which often result in long-term expression of the inserted transgene. Lentiviral vectors are retroviral vectors that can transduce or infect non-dividing cells and typically produce high viral titers. If transient expression is desired, adenovirus based systems may be used. Adenoviral based vectors can have very high transduction efficiencies in many cell types and do not require cell division.

In some embodiments, administration comprises administration by electroporation. In some embodiments, administration comprises administration by nanoparticle delivery. In some embodiments, administration comprises administration by liposomal delivery. Any effective route of administration can be used to administer an effective amount of a pharmaceutical composition described herein.

In some embodiments, administration comprises administration by other non-viral delivery of nucleic acids. Exemplary non-viral delivery methods include, but are not limited to, RNP complexes, lipofection, nucleofection, microinjection, biolistics, virosomes, liposomes, immunoliposomes, polycations or liponucleic acid conjugates, naked DNA, artificial virions , and agent-enhanced uptake of DNA. Lipofection is described in, for example, U.S. Patent Nos. 5,049,386, 4,946,787; and 4,897,355, and lipofection reagents are commercially available (eg, Transfectam™ and Lipofectin™). Cationic and neutral lipids suitable for efficient receptor-recognition lipofection of polynucleotides are described in Freigner, WO1991/17424; Including those of WO 1991/16024. Delivery can be to cells (eg, in vitro or ex vivo administration) or target tissues (eg, in vivo administration).

As used herein, the term “subject” refers to any individual for whom diagnosis, treatment or therapy is sought. In some embodiments, the subject is an animal. In some embodiments, the subject is a mammal. In some embodiments, the subject is a human.

Efficacy of treatment can be determined by a skilled clinician. However, treatment is one in which any or all of the signs or symptoms of the disease or disorder are altered in a beneficial manner (eg, reduced by at least 10%), or other clinically acceptable symptoms or markers of the disease are improved or ameliorated. In this case, it is considered "effective treatment". Efficacy can also be measured by the subject's failure to deteriorate (eg, stopping or at least slowing the progression of the disease) as assessed by the need for hospitalization or medical intervention. Methods for measuring these indicators are known to those skilled in the art. Treatment may include (1) inhibition of the disease, eg arresting or slowing the progression of symptoms; or (2) alleviation of the disease, eg causing regression of symptoms; and (3) preventing or reducing the likelihood of a symptom occurring.

An RGN polypeptide disclosed herein or a polynucleotide encoding the same, a gRNA disclosed herein or a polynucleotide encoding the same, a deaminase disclosed herein or a polynucleotide encoding the same, a fusion protein disclosed herein, a system disclosed herein (e.g., a fusion proteins), ribonucleoprotein complexes or cells, gRNA or gRNA-encoding polynucleotides, fusion protein-encoding polynucleotides, or systems disclosed herein comprising any RGN polypeptide or RGN-encoding polynucleotide, and pharmaceuticals Pharmaceutical compositions comprising an acceptable carrier are provided.

As used herein, a "pharmaceutically acceptable carrier" is a substance that does not cause significant irritation to an organism and does not abrogate the activity and properties of an active ingredient (eg, a deaminase or fusion protein or nucleic acid molecule encoding it). refers to The carrier must be of sufficiently high purity and sufficiently low toxicity to render it suitable for administration to the subject being treated. The carrier may be inert or may have pharmaceutical benefits. In some embodiments, the pharmaceutically acceptable carrier comprises one or more compatible solid or liquid fillers, diluents or encapsulating materials suitable for administration to humans or other vertebrates. In some embodiments, the pharmaceutical composition includes a pharmaceutically acceptable carrier that is non-naturally occurring. In some embodiments, the pharmaceutically acceptable carrier and active ingredient are not found together in nature and are therefore heterogeneous.

Pharmaceutical compositions used in the methods disclosed herein may be formulated with suitable carriers, excipients and other agents that provide suitable delivery, tolerance, and the like. A number of suitable formulations are known to those skilled in the art. See, eg, Remington, The Science and Practice of Pharmacy (21st ed. 2005). Non-limiting examples include sterile diluents such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerin, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl paraben; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid; buffers such as acetate, citrate or phosphate and tonicity adjusting agents such as sodium chloride or dextrose. A particular carrier administered intravenously is physiological saline or phosphate buffered saline (PBS). Pharmaceutical compositions for oral or parenteral use may be prepared in unit dose dosage forms adapted to the dosage of the active ingredient. Such dosage forms in unit doses include, for example, tablets, pills, capsules, injections (ampoules), suppositories and the like. These compositions may also contain adjuvants including preservatives, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms can be ensured by various antibacterial and antifungal agents, such as parabens, chlorobutanol, phenol, sorbic acid and the like. It may also be desirable to include isotonic agents such as sugars, sodium chloride, and the like. Prolonged absorption of the injectable pharmaceutical form may be brought about by the use of agents which delay absorption, for example, aluminum monostearate and gelatin.

In some embodiments where a cell comprising or modified with an RGN, gRNA, deaminase, fusion protein, system (including one comprising a fusion protein) or polynucleotide encoding the same disclosed herein is administered to a subject, the cell is It is administered as a suspension with an acceptable carrier. One skilled in the art will appreciate that a pharmaceutically acceptable carrier to be used in a cell composition will not contain a buffer, compound, cryoprotectant, preservative or other agent in an amount that substantially interferes with the viability of cells to be delivered to a subject. will be. Formulations comprising cells may include, for example, osmotic buffers to maintain cell membrane integrity, and optionally nutrients to maintain cell viability or enhance engraftment upon administration. Such formulations and suspensions are known to those skilled in the art and/or can be adapted for use with the cells described herein using routine experimentation.

The cell composition may also be emulsified or provided as a liposomal composition, provided that the emulsification procedure does not adversely affect cell viability. The cells and any other active ingredient can be mixed with excipients that are pharmaceutically acceptable and compatible with the active ingredient in amounts suitable for use in the methods of treatment described herein.

Additional agents included in the cell composition may include pharmaceutically acceptable salts of components therein. Pharmaceutically acceptable salts include acid addition salts (formed with the free amino groups of the polypeptide) formed with inorganic acids such as, for example, hydrochloric acid or phosphoric acid, or organic acids such as acetic acid, tartaric acid, mandelic acid, and the like. Salts formed with free carboxyl groups can also be formed with inorganic bases such as, for example, sodium, potassium, ammonium, calcium or ferric hydroxides, and organic bases such as isopropylamine, trimethylamine, 2-ethylamino ethanol, histidine, procaine, and the like. can be derived from

Suitable routes of administration of the pharmaceutical compositions described herein include, but are not limited to, topical, subcutaneous, transdermal, intradermal, intralesional, intraarticular, intraperitoneal, intravesical, transmucosal, gingival, intradental, intracochlear, intraoral, intratracheal, This includes epidural, intrathecal, intramuscular, intravenous, intravascular, intraosseous, periocular, intratumoral, intracerebral and intraventricular administration.

In some embodiments, a pharmaceutical composition described herein is administered topically to an affected site (eg, lung). In some embodiments, a pharmaceutical composition described herein is administered to a subject by injection, inhalation (eg, inhalation of an aerosol), by catheter, by suppository, or by implant, wherein the implant is a membrane, such as It is a porous, non-porous or gelatinous material containing sialastic membranes or fibers. In some embodiments, the pharmaceutical composition is formulated for delivery to a subject, eg, for gene editing.

In some embodiments, the pharmaceutical composition is formulated according to conventional procedures as a composition adapted for intravenous or subcutaneous administration to a subject, eg, a human. In some embodiments, pharmaceutical compositions for administration by injection are solutions in sterile isotonic aqueous buffer. If necessary, the pharmaceutical may also include a solubilizing agent and a local anesthetic such as lignocaine to relieve pain at the injection site. Generally, the ingredients are supplied individually or mixed together as a dry lyophilized powder or water free concentrate in a hermetically sealed container such as an ampoule or sachet indicating the amount of active agent. If the pharmaceutical is to be administered by infusion, it can be dispensed with an infusion bottle containing sterile pharmaceutical grade water or saline. Where the pharmaceutical composition is administered by injection, an ampoule of sterile water for injection or saline may be provided so that the ingredients may be mixed prior to administration.

In some embodiments, the pharmaceutical composition may be contained within lipid particles or vesicles such as liposomes or microcrystals, which are also suitable for parenteral administration.

Although the description of pharmaceutical compositions provided herein primarily relates to pharmaceutical compositions suitable for administration to humans, those skilled in the art will appreciate that such compositions are generally suitable for administration to animals or organisms of any kind.

Modification of causal mutations using base-editing

An example of a hereditary hereditary disease that can be corrected using an approach that relies on the RGN-deaminase fusion proteins of the present invention is cystic fibrosis. Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene (represented by SEQ ID NO: 51). CFTR encodes a cAMP-regulated chloride channel located in the apical membrane of epithelial cells that catalyzes the passage of small ions across the membrane. Dysregulation of this mechanism causes impairment of salt and fluid homeostasis, which leads to multi-organ dysfunction and ultimately mortality from respiratory failure.

Nearly 2,000 mutations in the CFTR gene have been found to cause CF. CFTR mutations are divided into six classes based on functional defects in CFTR protein synthesis, trafficking, function or stability, but it is recognized that many CFTR mutants exhibit multiple defects. Class I mutations result in severely defective protein production. These are primarily nonsense or frameshift mutations that introduce a premature stop codon (PTC) leading to unstable messenger RNA (mRNA) that is degraded by the mRNA decay pathway (NMD). Nonsense mutations due to single nucleotide changes comprise a major subset of class I mutations (Marangi, M. and Pistritto, G, 2018, Front Pharmacol 9, 396, doi:10.3389/fphar.2018.00396; Pranke, I. , et al., 2019, Front Pharmacol 10, 121, doi:10.3389/fphar.2019.00121], both of which are incorporated herein by reference). Because functional CFTR protein is not produced, treatment for patients with Class I cystic fibrosis can be difficult. In particular, a significant fraction of these nonsense mutations can potentially be addressed by A to G base editing agents (Geurts, M. H. et al., 2020, Cell Stem Cell 26, 503-510 e507, doi:10.1016/j. stem.2020.01.019], incorporated herein by reference).

Geurts et al. used a fusion protein comprising an adenine deaminase operably linked to RGN, i.e., SpyCas9 or xSpyCas9 variants, to perform precise base editing in cultured lung epithelial cells bearing a class I mutation from a cystic fibrosis patient. was the first group to do so. SpyCas9 recognized 5'-nGG-3'PAM, whereas the xSpyCas9 variant recognized reduced 5'-nG-3'. The authors note that a major limitation of the base editing technique is the PAM requirement of the Cas protein used. They found that the majority of nonsense mutations identified in the CFTR gene were not within the targeting window required for fusion proteins containing RGN SpyCas9. A PAM is a short motif, usually 1 to 4 nucleotides, on a target DNA sequence recognized by RGN. The PAM sequence is unique to each RGN protein, allowing the RGN to access only the genomic space around the appropriate PAM. Additionally, the base editing window for base editing agents is frequently limited to only a portion of the nucleotides in the target sequence. If the nucleotide of interest is too close to the PAM, the RGN blocks access to the nucleotide. If the nucleotide is too far from the PAM, the deaminase tethered to the RGN cannot reach the nucleotide. Also, the amount of ssDNA exposed by the R-loop limits the accessibility of deaminase. The present invention includes an RGN-deaminase fusion protein wherein RGN recognizes a PAM proximal to a class I mutation in the CFTR gene and the deaminase can successfully modify the targeted causative mutation.

Another limitation of RGN-deaminase fusion proteins known in the art is that the vector construct encoding the fusion protein is too large for in vivo delivery methods. AAV delivery of these fusion proteins is not an option for SpyCas9-based fusion proteins because their size exceeds the limit for efficient AAV packaging. The RGN component of the fusion proteins described herein is smaller in size and thus is a viable candidate for AAV vector delivery strategies. The present invention also discloses guide RNAs specific for the RGNs described herein and guiding the fusion proteins of the present invention to target sites of previously unreachable nonsense mutations in the CFTR gene. The present invention also teaches methods of using the fusion proteins for targeted base editing via AAV vector delivery in vivo.

Ideally, both the coding sequence of the RGN-deaminase fusion protein of the present invention and the corresponding guide RNA for targeting the fusion protein to the CFTR gene can be packaged into a single AAV vector. The generally accepted size limit for AAV vectors is 4.7 kb, but larger sizes can be considered with reduced packing efficiency. The RGN nickases of Table 28 have a coding sequence length of about 3.15-3.45 kB. To ensure that expression cassettes for both the fusion protein and its corresponding guide RNA can be fitted into AAV vectors, novel active deletion variants of RGN are described herein. In addition to shortening the amino acid sequence of the RGN of the fusion protein and thus the coding sequence, the peptide linker connecting the RGN and the deaminase can also be shortened. Finally, genetic elements, such as promoters, enhancers, and/or terminators, can also be engineered through deletion assays to determine the minimum size required for each to be functional.

Some embodiments of the present disclosure provide methods of editing nucleic acids using the deaminase or RGN complex described herein to achieve a nucleobase change, e.g., A:T base pairing to G:C base pairing. In some embodiments, the method is a method of editing the nucleobases of a nucleic acid (eg, base pairs of a double-stranded DNA sequence). In some embodiments, a deaminase or RGN complex described herein is used to introduce point mutations into nucleic acids by deamination and excision of the target “A” nucleobase. In some embodiments, deamination-and-ablation of a target nucleobase results in correction of a genetic defect, eg, correction of a point mutation in the CFTR gene. In some embodiments, the genetic defect is associated with a disease, disorder or condition, such as cystic fibrosis. For example, in some embodiments, to correct a gene associated with a genetic defect (eg, in the treatment of a proliferative disorder), for example to correct a point mutation in the CFTR gene, SEQ ID NO: Provided herein are methods of using a base edited RGN complex comprising a fusion protein with a deaminase having an amino acid sequence that is at least 80% identical to the sequence set forth in any one of 399 and 405-407. In a specific embodiment, the target sequence within the CFTR gene is 62-97, 116-139, 152-185, 203-234, 251-286, 305-344, 562, or 563.

In some embodiments, the purpose of the methods provided herein is to restore function of a dysfunctional gene through genome editing. Base editing proteins provided herein can be validated for gene editing-based human therapeutics in vitro, for example, by correcting disease-associated mutations in human cell culture. A fusion protein provided herein comprising a nucleic acid binding protein (eg, nCas9) and a nucleobase modification domain (eg, a deaminase having an amino acid sequence set forth in SEQ ID NO: 407, 399 or 405) and/or It will be appreciated by those skilled in the art that the RGN complex can be used to correct any single point from T to G or to change the T:A to G:C pairing.

In some embodiments, provided herein are methods of treating a subject diagnosed with a disease associated with or caused by a point mutation (eg, a mutation in the CFTR gene) that can be corrected by a fusion protein or RGN complex described herein. Provided. For example, in some embodiments, administering to a subject having such a disease, e.g., cystic fibrosis, an effective amount of a fusion protein or RGN complex disclosed herein that corrects a point mutation or introduces a deactivating mutation into a disease-associated gene A method including that is provided. In some embodiments, in a subject having a cancer associated with such a disease, e.g., a point mutation as described above, a fusion protein, RGN complex, or a fusion protein disclosed herein that corrects a point mutation or introduces a deactivating mutation into a disease-associated gene. Methods comprising administering an effective amount of a pharmaceutical composition are provided. In a specific embodiment, a method of treating cystic fibrosis is provided along with a method of reducing at least one symptom of cystic fibrosis by administering an effective amount of a pharmaceutical composition disclosed herein. An effective amount of the pharmaceutical composition for treating or reducing the symptoms of cystic fibrosis can reduce symptoms of cystic fibrosis by about 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50% compared to control patients. , 60%, 70%, 80%, 90%, at least 95%; or about 10-20%, 15-25%, 20-40%, 30-50%, 40-60%, 50-70%, 60-80%, 70-90%, 80-95%, or 90-90%. can be reduced (i.e. cured) by 95%. In a specific embodiment, the control patient can be the same patient prior to administration of an effective amount of a pharmaceutical composition disclosed herein. Symptoms of cystic fibrosis include sneezing, persistent cough that produces mucus or mucus, shortness of breath, especially with exertion, recurrent lung infections, nasal congestion, nasal congestion, sinuses, greasy and foul-smelling stools, constipation, nausea, abdominal swelling, and loss of appetite. may include, but are not limited to, loss. Methods for identifying and measuring symptoms of cystic fibrosis are known in the art.

In some embodiments of the described methods of modifying a target DNA molecule, the contacting step is performed in vitro. In certain embodiments, the contacting step is performed in vivo. In some embodiments, the contacting step is performed on a subject (eg, a human subject or a non-human animal subject). In some embodiments, the contacting step is performed on a cell, such as a human or non-human animal cell.

XII. Cells containing polynucleotide gene modification

Provided herein are cells and organisms comprising a target nucleic acid molecule of interest modified using a process mediated by a fusion protein, optionally with a gRNA, as described herein. In some embodiments, the fusion protein comprises a deaminase polypeptide comprising the amino acid sequence of any of SEQ ID NOs: 1-10 and 399-441, or an active variant or fragment thereof. In some embodiments, the fusion protein is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80% relative to any of SEQ ID NOs: 1-10 and 399-441. %, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identity. In some embodiments, the fusion protein comprises a deaminase and a DNA-binding polypeptide (eg, an RNA-guided, DNA-binding polypeptide). In a further embodiment, the fusion protein comprises a deaminase and RGN or a variant thereof, such as eg APG07433.1 (SEQ ID NO: 41) or its nickase variant nAPG07433.1 (SEQ ID NO: 42). In some embodiments, the fusion protein comprises a deaminase and Cas9 or a variant thereof, such as eg dCas9 or the nickase Cas9. In some embodiments, the fusion protein comprises a nuclease-inactive or nickase variant of a type II CRISPR-Cas polypeptide. In some embodiments, the fusion protein comprises a nuclease-inactive or nickase variant of a type V CRISPR-Cas polypeptide. In some embodiments, the fusion protein comprises a nuclease-inactive or nickase variant of a Type VI CRISPR-Cas polypeptide.

Transformed cells may be eukaryotic (eg, mammalian, plant, insect, avian cells) or prokaryotic. Also provided are organelles and embryos comprising at least one nucleotide sequence modified by a process using a fusion protein as described herein. Genetically modified cells, organisms, organelles and embryos may be heterozygous or homozygous for the modified nucleotide sequence. Mutation(s) introduced by the deaminase domain of the fusion protein may result in altered expression (up-regulation or down-regulation), inactivation, or altered expression of the protein product or integrated sequence. When the mutation(s) result in inactivation of the gene or expression of a non-functional protein product, the genetically modified cell, organism, organelle or embryo is referred to as a “knockout”. A knockout phenotype may be the result of a deletion mutation (i.e., deletion of at least one nucleotide), an insertion mutation (i.e., insertion of at least one nucleotide), or a nonsense mutation (i.e., substitution of at least one nucleotide such that a stop codon is introduced) can

In some embodiments, the mutation(s) introduced by the deaminase domain of the fusion protein results in the production of a variant protein product. The expressed variant protein product may have at least one amino acid substitution and/or at least one amino acid addition or deletion. Variant protein products may exhibit altered characteristics or activities compared to wild-type proteins, such as, but not limited to, altered enzymatic activity or substrate specificity.

In some embodiments, the mutation(s) introduced by the deaminase domain of the fusion protein results in an altered expression pattern of the protein. As a non-limiting example, mutation(s) in a regulatory region that controls expression of a protein product can result in overexpression or downregulation of the protein product or an altered tissue or transient expression pattern.

Transformed cells can be grown into organisms, such as plants, in a conventional manner. See, eg, McCormick et al. (1986) Plant Cell Reports 5:81-84. These plants are then grown and pollinated with either the same modified strain or a different strain, and the resulting hybrid may have the genetic modification. The present invention provides genetically modified seeds. Progeny, variants and mutants of regenerative plants are also included within the scope of the present invention, provided that these portions include genetic modifications. Additionally, engineered plant products or by-products containing genetic modifications are provided, including, for example, soybean meal.

The methods provided herein can be used to transform any plant species, including but not limited to monocots and dicotyledons. Examples of plants of interest are corn (maize), sorghum, wheat, sunflower, tomato, cruciferous, pepper, potato, cotton, rice, soybean, sugar beet, sugar cane, tobacco, barley, and oilseed rape, Brassica species, alfalfa, Rye, millet, safflower, peanut, sweet potato, cassava, coffee, coconut, pineapple, citrus tree, cocoa, tea, banana, avocado, fig, guava, mango, olive, papaya, cashew, macadamia, almond, oat, vegetable, ornamental plants, and conifers, but are not limited thereto.

Vegetables include, but are not limited to, tomatoes, lettuce, green beans, lima beans, peas, and members of the genus Cucumis, such as cucumbers, cantaloupes, and muskmelons. Ornamental plants include, but are not limited to, azaleas, hydrangeas, hibiscus, roses, tulips, daffodils, petunias, carnations, poinsettias, and chrysanthemums. Preferably, the plant of the present invention is a crop plant (eg, maize, sorghum, wheat, sunflower, tomato, brassicaceae, pepper, potato, cotton, rice, soybean, sugar beet, sugar cane, tobacco, barley, oilseed rape etc.) is.

The methods provided herein may also be used to treat archaea and bacteria (e.g., Bacillus species, Klebsiella species, Streptomyces species, Rhizobium species, Escherichia species, Pseudomonas species, Salmonella species, Shigella species, Vibrio species, e.g. Lesinia species, Mycoplasma species, Agrobacterium and Lactobacillus species), including but not limited to, genetically modifying any prokaryotic species.

The methods provided herein can be used to genetically modify cells from or any eukaryotic species, including but not limited to animals (e.g., mammals, insects, fish, birds, and reptiles), fungi, amoebas, algae, and yeast. can be used to In some embodiments, a cell modified by a method disclosed herein is a cell of hematopoietic origin, such as a B cell, T cell, natural killer (NK) cell, pluripotent stem cell, induced pluripotent stem cell, chimeric antigen receptor T (CAR- T) immune cells (ie cells of the innate or adaptive immune system) including but not limited to cells, monocytes, macrophages and dendritic cells.

Modified cells can be introduced into organisms. These cells may originate from the same organism (eg, a human) in the case of autologous cell transplantation, wherein the cells are transformed with an ex vivo approach. In some embodiments, the cells are from another organism within the same species (eg, another human) in the case of allogeneic cell transplantation.

XIII. kit

Some aspects of the present disclosure provide kits comprising the deaminase of the present invention. In certain embodiments, the present disclosure provides deaminase and DNA-binding polypeptides of the invention (e.g., RNA-guided, DNA-binding polypeptides, such as RGN polypeptides, e.g., nuclease-inactive Cas9 domains). , and optionally a linker positioned between the DNA-binding polypeptide domain and the deaminase. In addition, in some embodiments, the kits include suitable reagents, buffers, and/or instructions for use of the fusion protein, eg, for DNA or RNA editing in vitro or in vivo. In some embodiments, the kit includes instructions for designing and using suitable gRNAs for targeted editing of nucleic acid sequences.

In some embodiments, the pharmaceutical composition comprises (a) a container containing a composition of the present disclosure in lyophilized form and (b) a second container containing a pharmaceutically acceptable diluent for injection (eg, sterile water). It may be provided as a pharmaceutical kit comprising Pharmaceutically acceptable diluents may be used to reconstitute or dilute the lyophilized compounds of the present disclosure. Such container(s) may optionally be associated with a notice in the form prescribed by a government agency regulating the manufacture, use, or sale of pharmaceutical or biological products, which notice is a government agency of manufacture, use, or sale for human administration. reflects the approval by

The singular articles (“a” and “an”) are used herein to refer to one or more than one (ie, at least one) of the grammatical objects of such an article. For example, "polypeptide" means one or more polypeptides.

All publications and patent applications mentioned herein are indicative of the level of skill of those skilled in the art to which this disclosure pertains. All publications and patent applications are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated herein by reference.

Although the foregoing invention has been described in some detail by way of examples and examples for clarity of understanding, it will be apparent that certain changes and modifications may be practiced within the scope of the appended claims.

Non-limiting embodiments include:

1. An amino acid sequence comprising an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441, and having deaminase activity. Isolated Polypeptide.

2. The isolation of embodiment 1 comprising an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 polypeptide.

3. The isolated protein of embodiment 1 comprising an amino acid sequence having 100% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441. polypeptide.

4. A nucleic acid molecule comprising a polynucleotide encoding a deaminase polypeptide, wherein the deaminase:

a) has at least 80% sequence identity to any one of SEQ ID NOs: 451, 449, 443, 11-20, 444-448, 450 and 452-485, or

b) encoding an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441

which is encoded by a nucleotide sequence

nucleic acid molecule.

5. The method of embodiment 4, wherein the deaminase is by a nucleotide sequence having at least 90% sequence identity to any one of SEQ ID NOs: 451, 449, 443, 11-20, 444-448, 450 and 452-485 A nucleic acid molecule that is encoded.

6. The method of embodiment 4, wherein the deaminase is by a nucleotide sequence having at least 95% sequence identity to any one of SEQ ID NOs: 451, 449, 443, 11-20, 444-448, 450 and 452-485 A nucleic acid molecule that is encoded.

7. The method of embodiment 4, wherein the deaminase is encoded by a nucleotide sequence having 100% sequence identity to any one of SEQ ID NOs: 451, 449, 443, 11-20, 444-448, 450 and 452-485 A nucleic acid molecule that is to be.

8. The method of embodiment 4, wherein the deaminase polypeptide is an amino acid having at least 95% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441. A nucleic acid molecule having a sequence.

9. The amino acid sequence of embodiment 4, wherein the deaminase polypeptide has 100% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441. A nucleic acid molecule having a.

10. The nucleic acid molecule of any one of embodiments 4-9, further comprising a heterologous promoter operably linked to said polynucleotide.

11. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a polypeptide of any one of embodiments 1-3 or a nucleic acid molecule of any one of embodiments 4-10.

12. The pharmaceutical composition according to embodiment 11, wherein the pharmaceutically acceptable carrier is heterologous to said polypeptide or said nucleic acid molecule.

13. The pharmaceutical composition according to embodiment 11 or 12, wherein the pharmaceutically acceptable carrier is not naturally-occurring.

14. A fusion comprising a DNA-binding polypeptide and a deaminase having at least 90% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 protein.

15. The method of embodiment 14, wherein the deaminase has at least 95% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441. fusion protein.

16. The fusion of embodiment 14, wherein said deaminase has 100% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 protein.

17. The fusion protein of any one of embodiments 14-16, wherein the deaminase is an adenine deaminase.

18. The fusion protein of any one of embodiments 14-17, wherein the DNA-binding polypeptide is a meganuclease, zinc finger fusion protein or TALEN.

19. The fusion protein of any one of embodiments 14-17, wherein the DNA-binding polypeptide is an RNA-guided, DNA-binding polypeptide.

20. The fusion protein of embodiment 19, wherein the RNA-guided, DNA-binding polypeptide is an RNA-guided nuclease (RGN) polypeptide.

21. The fusion protein of embodiment 20, wherein the RGN is a type II CRISPR-Cas polypeptide.

22. The fusion protein of embodiment 20, wherein the RGN is a type V CRISPR-Cas polypeptide.

23. The fusion protein of any one of embodiments 20-22, wherein the RGN is an RGN nickase.

24. The fusion protein of embodiment 20, wherein the RGN has an amino acid sequence with at least 95% sequence identity to any one of SEQ ID NOs: 41, 60, 366 and 368.

25. The fusion protein of embodiment 20, wherein the RGN has the amino acid sequence of any one of SEQ ID NOs: 41, 60, 366 and 368.

26. The fusion protein of embodiment 23, wherein the RGN nickase is any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398.

27. The fusion protein of any one of embodiments 14-26, further comprising one or more nuclear localization signals (NLS).

28. A nucleic acid molecule comprising a polynucleotide encoding a DNA-binding polypeptide and a fusion protein comprising a deaminase, wherein the deaminase:

a) has at least 80% sequence identity to any one of SEQ ID NOs: 451, 449, 443, 11-20, 444-448, 450 and 452-485, or

b) encoding an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441

which is encoded by a nucleotide sequence

nucleic acid molecule.

29. The nucleic acid of embodiment 28, wherein said nucleotide sequence has at least 90% sequence identity to any one of SEQ ID NOs: 451, 449, 443, 11-20, 444-448, 450 and 452-485. molecule.

30. The nucleic acid of embodiment 28, wherein said nucleotide sequence has at least 95% sequence identity to any one of SEQ ID NOs: 451, 449, 443, 11-20, 444-448, 450 and 452-485. molecule.

31. The nucleic acid molecule of embodiment 28, wherein said nucleotide sequence has 100% sequence identity to any one of SEQ ID NOs: 451, 449, 443, 11-20, 444-448, 450 and 452-485 .

32. The amino acid sequence of embodiment 28, wherein said nucleotide sequence has at least 95% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 A nucleic acid molecule that encodes.

33. The method of embodiment 28, wherein said nucleotide sequence is an amino acid sequence having 100% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 A nucleic acid molecule that encodes.

34. The nucleic acid molecule of any one of embodiments 28-33, wherein the deaminase is an adenine deaminase.

35. The nucleic acid molecule of any one of embodiments 28-34, wherein the DNA-binding polypeptide is a meganuclease, zinc finger fusion protein or TALEN.

36. The nucleic acid molecule of any one of embodiments 28-34, wherein the DNA-binding polypeptide is an RNA-guided, DNA-binding polypeptide.

37. The nucleic acid molecule of embodiment 36, wherein the RNA-guided, DNA-binding polypeptide is an RNA-guided nuclease (RGN) polypeptide.

38. The nucleic acid molecule of embodiment 37, wherein the RGN is a type II CRISPR-Cas polypeptide.

39. The nucleic acid molecule of embodiment 37, wherein the RGN is a type V CRISPR-Cas polypeptide.

40. The nucleic acid molecule of any one of embodiments 37-39, wherein the RGN is an RGN nickase.

41. The nucleic acid molecule of embodiment 37, wherein the RGN has an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 41, 60, 366 and 368.

42. The nucleic acid molecule of embodiment 37, wherein the RGN is SEQ ID NO: 41, 60, 366 or 368.

43. The nucleic acid molecule of embodiment 40, wherein the RGN nickase is any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398.

44. The nucleic acid molecule according to any one of embodiments 28-43, wherein the polynucleotide encoding the fusion protein is operably linked at its 5' end to a heterologous promoter.

45. The nucleic acid molecule according to any one of embodiments 28-44, wherein the polynucleotide encoding the fusion protein is operably linked at its 3' end to a heterologous terminator.

46. The nucleic acid molecule of any one of embodiments 28-45, wherein the fusion protein comprises one or more nuclear localization signals.

47. The nucleic acid molecule according to any one of embodiments 28-46, wherein the fusion protein is codon optimized for expression in a eukaryotic cell.

48. The nucleic acid molecule according to any one of embodiments 28-46, wherein the fusion protein is codon optimized for expression in prokaryotic cells.

49. A vector comprising the nucleic acid molecule of any one of embodiments 28-48.

50. A vector comprising the nucleic acid molecule of any one of embodiments 28-48, further comprising at least one nucleotide sequence encoding a guide RNA (gRNA) capable of hybridizing to a target sequence.

51. The vector of embodiment 50, wherein the gRNA is a single guide RNA.

52. The vector of embodiment 50, wherein the gRNA is a double guide RNA.

53. A cell comprising the fusion protein of any one of embodiments 14-27.

54. A cell comprising the fusion protein of any one of embodiments 14-27, and further comprising a guide RNA.

55. A cell comprising the nucleic acid molecule of any one of embodiments 28-48.

56. A cell comprising the vector of any one of embodiments 49-52.

57. The cell of any one of embodiments 53-56, which is a prokaryotic cell.

58. The cell of any one of embodiments 53-56, which is a eukaryotic cell.

59. The cell of embodiment 58, wherein the eukaryotic cell is a mammalian cell.

60. The cell of embodiment 59, wherein the mammalian cell is a human cell.

61. The cell of embodiment 60, wherein the human cell is an immune cell.

62. The cell of embodiment 61, wherein the immune cells are stem cells.

63. The cell of embodiment 62, wherein the stem cell is an induced pluripotent stem cell.

64. The cell of embodiment 58, wherein the eukaryotic cell is an insect or avian cell.

65. The cell of embodiment 58, wherein the eukaryotic cell is a fungal cell.

66. The cell of embodiment 58, wherein the eukaryotic cell is a plant cell.

67. A plant comprising the cells of embodiment 66.

68. A seed comprising the cell of embodiment 66.

69. A pharmaceutically acceptable carrier and the fusion protein of any one of embodiments 14-27, the nucleic acid molecule of any one of embodiments 28-48, the vector of any one of embodiments 49-52, or any one of embodiments 59-63 A pharmaceutical composition comprising either cell.

70. A method of producing a fusion protein comprising culturing a cell of any one of embodiments 53-66 under conditions in which the fusion protein is expressed.

71. Preparing a fusion protein comprising introducing the nucleic acid molecule of any one of embodiments 28-48 or the vector of any one of embodiments 49-52 into a cell and culturing the cell under conditions in which the fusion protein is expressed. method.

72. The method of embodiment 70 or 71 further comprising purifying said fusion protein.

73. The nucleic acid molecule comprising the nucleic acid molecule of any one of embodiments 37-43 and an expression cassette encoding the guide RNA, or the vector of any one of embodiments 50-52 is introduced into a cell, and the cell is A method for producing an RGN-fusion ribonucleoprotein complex, comprising culturing under conditions in which RGN-fusion ribonucleoprotein complex is expressed.

74. The method of embodiment 73, further comprising purifying said RGN fusion ribonucleoprotein complex.

75. A system for modifying a target DNA molecule comprising a target DNA sequence, comprising:

The system

a) an RNA-guided nuclease polypeptide (RGN) and a deaminase, wherein the deaminase is SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 a fusion protein having an amino acid sequence having at least 90% sequence identity to any one of, or a nucleotide sequence encoding the fusion protein; and

b) one or more guide RNAs capable of hybridizing to the target DNA sequence, or one or more nucleotide sequences encoding one or more guide RNAs (gRNAs)

contains;

Wherein the one or more guide RNAs are capable of forming a complex with the fusion protein to direct the fusion protein to bind to the target DNA sequence and modify the target DNA molecule.

system.

76. The amino acid sequence of embodiment 75, wherein said deaminase has at least 95% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 A system having

77. The method of embodiment 75, wherein the deaminase converts an amino acid sequence having 100% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441. system to have.

78. The system according to any one of embodiments 75-77, wherein at least one of the nucleotide sequence encoding the one or more guide RNAs and the nucleotide sequence encoding the fusion protein is operably linked to a promoter heterologous to the nucleotide sequence. .

79. The system of any one of embodiments 75-78, wherein the target DNA sequence is a eukaryotic target DNA sequence.

80. The system of any one of embodiments 75-79, wherein the target DNA sequence is located adjacent to a protospacer adjacent motif (PAM) recognized by RGN.

81. The system of any one of embodiments 75-80, wherein the target DNA molecule is within a cell.

82. The system of embodiment 81, wherein the cell is a eukaryotic cell.

83. The system of embodiment 82, wherein the eukaryotic cells are plant cells.

84. The system of embodiment 82, wherein the eukaryotic cells are mammalian cells.

85. The system of embodiment 84, wherein the mammalian cells are human cells.

86. The system of embodiment 85, wherein the human cells are immune cells.

87. The system of embodiment 86, wherein the immune cells are stem cells.

88. The system of embodiment 87, wherein the stem cells are induced pluripotent stem cells.

89. The system of embodiment 82, wherein the eukaryotic cells are insect cells.

90. The system of embodiment 81, wherein the cells are prokaryotic cells.

91. The system of any one of embodiments 75-90, wherein the RGN of the fusion protein is a type II CRISPR-Cas polypeptide.

92. The system of any one of embodiments 75-90, wherein the RGN of the fusion protein is a type V CRISPR-Cas polypeptide.

93. The system of any one of embodiments 75-90, wherein the RGN of the fusion protein has an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 41, 60, 366 or 368.

94. The system of any one of embodiments 75-90, wherein the RGN of the fusion protein has the amino acid sequence of any one of SEQ ID NOs: 41, 60, 366 and 368.

95. The system of any one of embodiments 75-90, wherein the RGN of the fusion protein is an RGN nickase.

96. The system of embodiment 95, wherein the RGN nickase is any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398.

97. The system of any one of embodiments 75-96, wherein the fusion protein comprises one or more nuclear localization signals.

98. The system of any one of embodiments 75-97, wherein the fusion protein is codon optimized for expression in a eukaryotic cell.

99. The system according to any one of embodiments 75-98, wherein the nucleotide sequence encoding the one or more guide RNAs and the nucleotide sequence encoding the fusion protein are located on one vector.

100. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the system of any one of embodiments 75-99.

101. A method of modifying a target DNA molecule comprising a target DNA sequence, comprising delivering a system according to any one of embodiments 75-99 to the target DNA molecule or a cell comprising the target DNA molecule how it would be.

102. The method of embodiment 101, wherein the modified target DNA molecule comprises an A>N mutation of at least one nucleotide in the target DNA molecule, wherein N is C, G or T.

103. The method of embodiment 102, wherein said modified target DNA molecule comprises an A>G mutation of at least one nucleotide in the target DNA molecule.

104. A method of modifying a target DNA molecule comprising a target sequence, comprising:

a) under conditions suitable for the formation of an RNA-guided nuclease polypeptide (RGN)-deaminase ribonucleotide complex

i) one or more guide RNAs capable of hybridizing to a target DNA sequence; and

ii) RGN and at least one deaminase, wherein the deaminase is at least 90 to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 A fusion protein having an amino acid sequence with % sequence identity

Assembling the RGN-deaminase ribonucleotide complex in vitro by combining; and

b) contacting the target DNA molecule or a cell containing the target DNA molecule with an in vitro-assembled RGN-deaminase ribonucleotide complex.

contains;

wherein the one or more guide RNAs hybridize to the target DNA sequence, thereby directing the fusion protein to bind to the target DNA sequence, and modification of the target DNA molecule occurs.

method.

105. The amino acid sequence of embodiment 104, wherein the deaminase has at least 95% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441. How to have.

106. The method of embodiment 104, wherein the deaminase converts an amino acid sequence having 100% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441. How to have.

107. The method according to any one of embodiments 104-106, wherein said modified target DNA molecule comprises an A>N mutation of at least one nucleotide in the target DNA molecule, wherein N is C, G or T.

108. The method of embodiment 107, wherein said modified target DNA molecule comprises an A>G mutation of at least one nucleotide in the target DNA molecule.

109. The method of any one of embodiments 104-108, wherein the RGN of the fusion protein is a type II CRISPR-Cas polypeptide.

110. The method of any one of embodiments 104-108, wherein the RGN of the fusion protein is a type V CRISPR-Cas polypeptide.

111. The method of any one of embodiments 104-108, wherein the RGN of the fusion protein has an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 41, 60, 366 or 368.

112. The method of any one of embodiments 104-108, wherein the RGN of the fusion protein has the amino acid sequence of any one of SEQ ID NOs: 41, 60, 366 and 368.

113. The method of any one of embodiments 104-108, wherein the RGN of the fusion protein is an RGN nickase.

114. The method of embodiment 113, wherein the RGN nickase is any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398.

115. The method of any one of embodiments 104-114, wherein the fusion protein comprises one or more nuclear localization signals.

116. The method of any one of embodiments 104-115, wherein the fusion protein is codon optimized for expression in a eukaryotic cell.

117. The method of any one of embodiments 104-116, wherein said target DNA sequence is a eukaryotic target DNA sequence.

118. The method according to any one of embodiments 104-117, wherein said target DNA sequence is located adjacent to a protospacer adjacent motif (PAM).

119. The method of any one of embodiments 104-118, wherein the target DNA molecule is within a cell.

120. The method of embodiment 119, wherein the cell is a eukaryotic cell.

121. The method of embodiment 120, wherein the eukaryotic cell is a plant cell.

122. The method of embodiment 120, wherein the eukaryotic cell is a mammalian cell.

123. The method of embodiment 122, wherein the mammalian cells are human cells.

124. The method of embodiment 123, wherein the human cells are immune cells.

125. The method of embodiment 124, wherein the immune cells are stem cells.

126. The method of embodiment 125, wherein the stem cells are induced pluripotent stem cells.

127. The method of embodiment 120, wherein the eukaryotic cells are insect cells.

128. The method of embodiment 119, wherein the cell is a prokaryotic cell.

129. The method of any one of embodiments 119-128, further comprising selecting a cell comprising said modified DNA molecule.

130. A cell comprising a modified target DNA sequence according to the method of embodiment 129.

131. The cell of embodiment 130, which is a eukaryotic cell.

132. The cell of embodiment 131, wherein the eukaryotic cell is a plant cell.

133. A plant comprising the cell of embodiment 132.

134. A seed comprising the cell of embodiment 132.

135. The cell of embodiment 131, wherein the eukaryotic cell is a mammalian cell.

136. The cell of embodiment 135, wherein the mammalian cell is a human cell.

137. The cell of embodiment 136, wherein the human cell is an immune cell.

138. The cell of embodiment 137, wherein the immune cells are stem cells.

139. The cell of embodiment 138, wherein the stem cells are induced pluripotent stem cells.

140. The cell of embodiment 131, wherein the eukaryotic cell is an insect cell.

141. The cell of embodiment 130, which is a prokaryotic cell.

142. A pharmaceutical composition comprising the cells of any one of embodiments 135-139 and a pharmaceutically acceptable carrier.

143. A method for producing genetically modified cells by correction of mutations causative for genetic hereditary disorders, comprising:

The method is

a) an RNA-guided nuclease polypeptide (RGN) and a deaminase, wherein the deaminase is SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 A fusion protein having an amino acid sequence having at least 90% sequence identity to any one of, or a polynucleotide encoding the fusion protein, wherein the polynucleotide encoding the fusion protein is capable of expressing the fusion protein in a cell. a polynucleotide operably linked to a promoter that allows; and

b) at least one guide RNA (gRNA) capable of hybridizing to a target DNA sequence, or a polynucleotide encoding said gRNA, wherein said polynucleotide encoding a gRNA is operable to a promoter enabling expression of the gRNA in a cell. Polynucleotides that are closely linked

Including introducing a;

Whereby the fusion protein and gRNA target the genomic location of the causative mutation and modify the genomic sequence to remove the causative mutation.

method.

144. The amino acid sequence of embodiment 143, wherein said deaminase has at least 95% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 How to have.

145. The method of embodiment 143, wherein the deaminase converts an amino acid sequence having 100% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441. How to have.

146. The method of any one of embodiments 143-145, wherein the RGN of the fusion protein is an RGN nickase.

147. The method of embodiment 146, wherein the RGN nickase is any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398.

148. The method of any one of embodiments 143-147, wherein the genomic modification comprises introducing an A>G mutation of at least one nucleotide in the target DNA sequence.

149. The method of any one of embodiments 143-148, wherein the cells are animal cells.

150. The method of embodiment 149, wherein the animal cells are mammalian cells.

151. The method of embodiment 150, wherein the cell is from a dog, cat, mouse, rat, rabbit, horse, sheep, goat, cow, pig or human.

152. The method of any one of embodiments 143-151, wherein correcting the causal mutation comprises correcting a nonsense mutation.

153. The method of embodiment 149, wherein the genetic hereditary disease is a disease listed in Table 34.

154. The method of embodiment 149, wherein the genetic hereditary disease is cystic fibrosis.

155. The method of embodiment 154, wherein the gRNA is any one of SEQ ID NOs: 62-97, 116-139, 152-185, 203-234, 251-286, 305-344, 562 and 563, or the complement thereof The method further comprises a targeting spacer sequence.

156. The method of embodiment 155, wherein the gRNA comprises any one of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564.

157. A CRISPR RNA (crRNA) or a nucleic acid molecule encoding it, wherein said CRISPR RNA comprises a spacer sequence that targets a target DNA sequence within a cystic fibrosis transmembrane conductance regulator (CFTR) gene, wherein said target sequence comprises a sequence ID: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364, 562, and 563, or a CRISPR RNA (crRNA) having a sequence set forth in any one of ) or a nucleic acid molecule encoding it.

158. A guide RNA comprising the crRNA of embodiment 157.

159. The guide RNA according to embodiment 158, which is a dual-guide RNA.

160. The guide RNA according to embodiment 158, which is a single guide RNA (sgRNA).

161. The method of embodiment 160, wherein said sgRNA has at least 90% sequence identity to any one of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564 A guide RNA having a.

162. The method of embodiment 160, wherein said sgRNA has at least 95% sequence identity to any one of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564 A guide RNA having a.

163. The guide of embodiment 160, wherein said sgRNA has a sequence set forth in any one of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564 RNA.

164. A vector comprising one or more nucleic acid molecules encoding said guide RNA of any one of embodiments 158-163.

165. A system that binds to a target DNA sequence of a DNA molecule,

The system

a) one or more polynucleotides comprising one or more nucleotide sequences encoding one or more guide RNAs, or one or more guide RNAs (gRNAs) capable of hybridizing to the target DNA sequence; and

b) a fusion protein comprising an RNA-guided nuclease polypeptide (RGN) and an adenine deaminase, or a polynucleotide comprising a nucleotide sequence encoding a fusion protein

contains;

wherein the one or more guide RNAs are capable of hybridizing to the target DNA sequence;

wherein the one or more guide RNAs are capable of forming a complex with the RGN polypeptide to direct the binding of the RGN polypeptide to the target DNA sequence of the DNA molecule;

wherein the at least one guide RNA comprises a CRISPR RNA (crRNA) comprising a spacer sequence that targets a target DNA sequence within a cystic fibrosis transmembrane conductance regulator (CFTR) gene, wherein the target sequence is SEQ ID NO: 98- 115, 140-151, 186-202, 235-250, 287-304, 345-364, 562, and 563, or the complement thereof.

system.

166. The system of embodiment 165, wherein at least one of the nucleotide sequence encoding the one or more guide RNAs and the nucleotide sequence encoding the fusion protein is operably linked to a promoter heterologous to the nucleotide sequence.

167. A system that binds to a target DNA sequence of a DNA molecule,

The system

a) one or more polynucleotides comprising one or more nucleotide sequences encoding one or more guide RNAs, or one or more guide RNAs (gRNAs) capable of hybridizing to the target DNA sequence; and

b) a fusion protein comprising an RNA-guided nuclease polypeptide (RGN) and an adenine deaminase

contains;

wherein the one or more guide RNAs are capable of hybridizing to the target DNA sequence;

wherein the one or more guide RNAs are capable of forming a complex with the RGN polypeptide to direct the binding of the RGN polypeptide to the target DNA sequence of the DNA molecule;

wherein the at least one guide RNA comprises a CRISPR RNA (crRNA) comprising a spacer sequence that targets a target DNA sequence within a cystic fibrosis transmembrane conductance regulator (CFTR) gene, wherein the target sequence is SEQ ID NO: 98- 115, 140-151, 186-202, 235-250, 287-304, 345-364, 562, and 563, or the complement thereof.

system.

168. The system according to embodiment 167, wherein at least one of the nucleotide sequences encoding said one or more guide RNAs is operably linked to a promoter heterologous to said nucleotide sequence.

169. The system of any one of embodiments 165-168, wherein the deaminase has an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 1-10 and 399-441.

170. The system of any one of embodiments 165-168, wherein the deaminase has an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 1-10 and 399-441.

171. The system of any one of embodiments 165-168, wherein the deaminase has an amino acid sequence having the sequence set forth in any one of SEQ ID NOs: 1-10 and 399-441.

172. The system according to any one of embodiments 165-171, wherein said RGN polypeptide and said one or more guide RNAs are not found complexed with each other in nature.

173. according to any one of embodiments 165-172,

a) the target DNA sequence is SEQ ID NOs: 62-68, 80-85, 116-119, 128-131, 163, 164, 180, 181, 203-209, 219-225, 256-258, 274-276 , 310-313, and 330-333, or the complement thereof, wherein the RGN polypeptide has a sequence having at least 90% sequence identity to SEQ ID NO:53;

b) the target DNA sequence is SEQ ID NOs: 68-71, 86-89, 120-122, 132-134, 152-156, 169-173, 213-215, 229-231, 251-255, 269-273 , 305-309, and 325-329, or the complement thereof, wherein the RGN polypeptide has a sequence having at least 90% sequence identity to SEQ ID NO:55;

c) the target DNA sequence has a sequence set forth in any one of SEQ ID NOs: 72, 73, 90, 91, 161, 162, 178, 179, 265, 266, 283, and 284, or the complement thereof, wherein the RGN the polypeptide has a sequence with at least 90% sequence identity to SEQ ID NO:52;

d) the target DNA sequence is SEQ ID NO: 74, 75, 92, 93, 123, 124, 135, 136, 167, 184, 216-218, 232-234, 259-261, 277-279, 314-317 , and the sequence set forth in any one of 334-337, or the complement thereof, wherein the RGN polypeptide has a sequence having at least 90% sequence identity to SEQ ID NO:56;

e) the target DNA sequence has a sequence set forth in any one of SEQ ID NOs: 76, 94, 210-212, 226-228, 322, 342, 562, and 563, or the complement thereof, wherein the RGN polypeptide comprises a sequence has a sequence with at least 90% sequence identity to ID: 42;

f) the target DNA sequence has a sequence set forth in any one of SEQ ID NOs: 77, 95, 125, 137, 157-160, 174-177, 323, and 343, or the complement thereof, wherein the RGN polypeptide comprises a sequence has a sequence with at least 90% sequence identity to ID: 54;

g) said target DNA sequence has a sequence set forth in any one of SEQ ID NOs: 78, 96, 126, 138, 168, 185, 267, 285, 318, 319, 338, and 339, or the complement thereof, wherein said The RGN polypeptide has a sequence with at least 90% sequence identity to SEQ ID NO:57;

h) the target DNA sequence has a sequence set forth in any one of SEQ ID NOs: 79, 97, 127, 139, 262-264, 280-282, 324 and 344, or the complement thereof, wherein the RGN polypeptide is SEQ ID NO: : has a sequence with at least 90% sequence identity to 58; or

i) the target DNA sequence has a sequence set forth in any one of SEQ ID NOs: 165, 166, 182, 183, 268, 286, 320, 321, 340 and 341, or the complement thereof, wherein the RGN polypeptide is sequence-identified having a sequence with at least 90% sequence identity to number: 59

system.

174. according to any one of embodiment 165-172,

a) the target DNA sequence is SEQ ID NOs: 62-68, 80-85, 116-119, 128-131, 163, 164, 180, 181, 203-209, 219-225, 256-258, 274-276 , 310-313, and 330-333, or the complement thereof, wherein said RGN polypeptide has a sequence with at least 95% sequence identity to SEQ ID NO:53;

b) the target DNA sequence is SEQ ID NOs: 68-71, 86-89, 120-122, 132-134, 152-156, 169-173, 213-215, 229-231, 251-255, 269-273 , 305-309, and 325-329, or the complement thereof, wherein said RGN polypeptide has a sequence with at least 95% sequence identity to SEQ ID NO:55;

c) the target DNA sequence has a sequence set forth in any one of SEQ ID NOs: 72, 73, 90, 91, 161, 162, 178, 179, 265, 266, 283, and 284, or the complement thereof, wherein the RGN the polypeptide has a sequence with at least 95% sequence identity to SEQ ID NO:52;

d) the target DNA sequence is SEQ ID NO: 74, 75, 92, 93, 123, 124, 135, 136, 167, 184, 216-218, 232-234, 259-261, 277-279, 314-317 , and the sequence set forth in any one of 334-337, or the complement thereof, wherein the RGN polypeptide has a sequence having at least 95% sequence identity to SEQ ID NO:56;

e) the target DNA sequence has a sequence set forth in any one of SEQ ID NOs: 76, 94, 210-212, 226-228, 322, 342, 562, and 563, or the complement thereof, wherein the RGN polypeptide comprises a sequence has a sequence with at least 95% sequence identity to ID: 42;

f) the target DNA sequence has a sequence set forth in any one of SEQ ID NOs: 77, 95, 125, 137, 157-160, 174-177, 323, and 343, or the complement thereof, wherein the RGN polypeptide comprises a sequence has a sequence with at least 95% sequence identity to ID: 54;

g) said target DNA sequence has a sequence set forth in any one of SEQ ID NOs: 78, 96, 126, 138, 168, 185, 267, 285, 318, 319, 338, and 339, or the complement thereof, wherein said The RGN polypeptide has a sequence with at least 95% sequence identity to SEQ ID NO:57;

h) the target DNA sequence has a sequence set forth in any one of SEQ ID NOs: 79, 97, 127, 139, 262-264, 280-282, 324 and 344, or the complement thereof, wherein the RGN polypeptide is SEQ ID NO: : has a sequence with at least 95% sequence identity to 58;

i) the target DNA sequence has a sequence set forth in any one of SEQ ID NOs: 165, 166, 182, 183, 268, 286, 320, 321, 340 and 341, or the complement thereof, wherein the RGN polypeptide is sequence-identified having a sequence with at least 95% sequence identity to number: 59

system.

175. according to any one of embodiments 165-172,

a) the target DNA sequence is SEQ ID NOs: 62-68, 80-85, 116-119, 128-131, 163, 164, 180, 181, 203-209, 219-225, 256-258, 274-276 , 310-313, and 330-333, or the complement thereof, wherein said RGN polypeptide has a sequence with 100% sequence identity to SEQ ID NO:53;

b) the target DNA sequence is SEQ ID NOs: 68-71, 86-89, 120-122, 132-134, 152-156, 169-173, 213-215, 229-231, 251-255, 269-273 , 305-309, and 325-329, or the complement thereof, wherein said RGN polypeptide has a sequence with 100% sequence identity to SEQ ID NO:55;

c) the target DNA sequence has a sequence set forth in any one of SEQ ID NOs: 72, 73, 90, 91, 161, 162, 178, 179, 265, 266, 283, and 284, or the complement thereof, wherein the RGN the polypeptide has a sequence with 100% sequence identity to SEQ ID NO:52;

d) the target DNA sequence is SEQ ID NO: 74, 75, 92, 93, 123, 124, 135, 136, 167, 184, 216-218, 232-234, 259-261, 277-279, 314-317 , and the sequence set forth in any one of 334-337, or the complement thereof, wherein said RGN polypeptide has a sequence with 100% sequence identity to SEQ ID NO:56;

e) the target DNA sequence has a sequence set forth in any one of SEQ ID NOs: 76, 94, 210-212, 226-228, 322, 342, 562, and 563, or the complement thereof, wherein the RGN polypeptide comprises a sequence has a sequence with 100% sequence identity to ID: 42;

f) the target DNA sequence has a sequence set forth in any one of SEQ ID NOs: 77, 95, 125, 137, 157-160, 174-177, 323, and 343, or the complement thereof, wherein the RGN polypeptide comprises a sequence has a sequence with 100% sequence identity to ID: 54;

g) said target DNA sequence has a sequence set forth in any one of SEQ ID NOs: 78, 96, 126, 138, 168, 185, 267, 285, 318, 319, 338, and 339, or the complement thereof, wherein said The RGN polypeptide has a sequence with 100% sequence identity to SEQ ID NO:57;

h) the target DNA sequence has a sequence set forth in any one of SEQ ID NOs: 79, 97, 127, 139, 262-264, 280-282, 324 and 344, or the complement thereof, wherein the RGN polypeptide is sequence-identified has a sequence with 100% sequence identity to number: 58;

i) the target DNA sequence has a sequence set forth in any one of SEQ ID NOs: 165, 166, 182, 183, 268, 286, 320, 321, 340 and 341, or the complement thereof, wherein the RGN polypeptide is sequence-identified having a sequence with 100% sequence identity to number: 59

system.

176. The system according to any one of embodiments 165-175, wherein at least one guide RNA is a dual-guide RNA.

177. The system of any one of embodiments 165-175, wherein at least one guide RNA is a single guide RNA (sgRNA).

178. according to embodiment 177,

a) the sgRNA has at least 90% sequence identity to any one of SEQ ID NOs: 98-104, 140-143, 197, 198, 235-241, 292-294, and 350-353, wherein the RGN polypeptide has a sequence with at least 90% sequence identity to SEQ ID NO:53;

b) the sgRNA has at least 90% sequence identity to any one of SEQ ID NOs: 104-107, 144-146, 186-190, 245-247, 287-291, and 345-349, wherein the RGN polypeptide has a sequence with at least 90% sequence identity to SEQ ID NO:55;

c) the sgRNA has at least 90% sequence identity to any one of SEQ ID NOs: 108, 109, 195, 196, 301 and 302, wherein the RGN polypeptide has at least 90% sequence identity to SEQ ID NO: 52 has a sequence having;

d) said sgRNA has at least 90% sequence identity to any one of SEQ ID NOs: 110, 111, 147, 148, 201, 248-250, 295-297 and 354-357, wherein said RGN polypeptide is sequence-identified has a sequence with at least 90% sequence identity to number: 56;

e) the sgRNA has at least 90% sequence identity to any one of SEQ ID NOs: 112, 242-244, 362, and 564, and wherein the RGN polypeptide has at least 90% sequence identity to SEQ ID NO: 42 have a sequence with;

f) the sgRNA has at least 90% sequence identity to any one of SEQ ID NOs: 113, 149, 191-194, and 363, and wherein the RGN polypeptide has at least 90% sequence identity to SEQ ID NO: 54 have a sequence with;

g) the sgRNA has at least 90% sequence identity to any one of SEQ ID NOs: 114, 150, 202, 303, 358, and 359, wherein the RGN polypeptide has at least 90% sequence identity to SEQ ID NO: 57 have sequences with identity;

h) said sgRNA has at least 90% sequence identity to any one of SEQ ID NOs: 115, 151, 298-300 and 364, and wherein said RGN polypeptide has at least 90% sequence identity to SEQ ID NO: 58 have a sequence;

i) the sgRNA has at least 90% sequence identity to any one of SEQ ID NOs: 199, 200, 304, 360 and 361, and wherein the RGN polypeptide has at least 90% sequence identity to SEQ ID NO: 59 having a sequence

system.

179. according to embodiment 177,

a) the sgRNA has at least 95% sequence identity to any one of SEQ ID NOs: 98-104, 140-143, 197, 198, 235-241, 292-294, and 350-353, wherein the RGN polypeptide has a sequence with at least 95% sequence identity to SEQ ID NO:53;

b) the sgRNA has at least 95% sequence identity to any one of SEQ ID NOs: 104-107, 144-146, 186-190, 245-247, 287-291, and 345-349, wherein the RGN polypeptide has a sequence with at least 95% sequence identity to SEQ ID NO:55;

c) the sgRNA has at least 95% sequence identity to any one of SEQ ID NOs: 108, 109, 195, 196, 301 and 302, wherein the RGN polypeptide has at least 95% sequence identity to SEQ ID NO: 52 has a sequence having;

d) said sgRNA has at least 95% sequence identity to any one of SEQ ID NOs: 110, 111, 147, 148, 201, 248-250, 295-297 and 354-357, wherein said RGN polypeptide is sequence-identified has a sequence with at least 95% sequence identity to number: 56;

e) the sgRNA has at least 95% sequence identity to any one of SEQ ID NOs: 112, 242-244, 362 and 564, and wherein the RGN polypeptide has at least 95% sequence identity to SEQ ID NO: 42 have a sequence;

f) the sgRNA has at least 95% sequence identity to any one of SEQ ID NOs: 113, 149, 191-194, and 363, and wherein the RGN polypeptide has at least 95% sequence identity to SEQ ID NO: 54 have a sequence with;

g) the sgRNA has at least 95% sequence identity to any one of SEQ ID NOs: 114, 150, 202, 303, 358, and 359, wherein the RGN polypeptide has at least 95% sequence identity to SEQ ID NO: 57 have sequences with identity;

h) said sgRNA has at least 95% sequence identity to any one of SEQ ID NOs: 115, 151, 298-300 and 364, and wherein said RGN polypeptide has at least 95% sequence identity to SEQ ID NO: 58 have a sequence;

i) the sgRNA has at least 95% sequence identity to any one of SEQ ID NOs: 199, 200, 304, 360 and 361, and wherein the RGN polypeptide has at least 95% sequence identity to SEQ ID NO: 59 having a sequence

system.

180. according to embodiment 177,

a) the sgRNA has 100% sequence identity to any one of SEQ ID NOs: 98-104, 140-143, 197, 198, 235-241, 292-294, and 350-353, wherein the RGN polypeptide has a sequence with 100% sequence identity to SEQ ID NO: 53;

b) the sgRNA has 100% sequence identity to any one of SEQ ID NOs: 104-107, 144-146, 186-190, 245-247, 287-291, and 345-349, wherein the RGN polypeptide has a sequence has a sequence with 100% sequence identity with identification number: 55;

c) the sgRNA has 100% sequence identity to any one of SEQ ID NOs: 108, 109, 195, 196, 301 and 302, and wherein the RGN polypeptide has 100% sequence identity to SEQ ID NO: 52 have a sequence;

d) said sgRNA has 100% sequence identity to any one of SEQ ID NOs: 110, 111, 147, 148, 201, 248-250, 295-297 and 354-357, wherein said RGN polypeptide is SEQ ID NO: : has a sequence with 100% sequence identity with 56;

e) the sgRNA has 100% sequence identity to any one of SEQ ID NOs: 112, 242-244, 362 and 564, and wherein the RGN polypeptide has 100% sequence identity to SEQ ID NO: 42. have;

f) the sgRNA has 100% sequence identity to any one of SEQ ID NOs: 113, 149, 191-194 and 363, and wherein the RGN polypeptide has 100% sequence identity to SEQ ID NO: 54. have;

g) a sequence wherein said sgRNA has 100% sequence identity to any one of SEQ ID NOs: 114, 150, 202, 303, 358 and 359, and wherein said RGN polypeptide has 100% sequence identity to SEQ ID NO: 57; have;

h) the sgRNA has 100% sequence identity to any one of SEQ ID NOs: 115, 151, 298-300 and 364, and wherein the RGN polypeptide has 100% sequence identity to SEQ ID NO: 58. have;

i) wherein the sgRNA has 100% sequence identity to any one of SEQ ID NOs: 199, 200, 304, 360 and 361, and wherein the RGN polypeptide has 100% sequence identity to SEQ ID NO: 59; to have

system.

181. A cell comprising the crRNA or nucleic acid molecule of embodiment 157, the guide RNA of any one of embodiments 158-163, the vector of embodiment 164 or the system of any one of embodiments 165-180.

182. The crRNA or nucleic acid molecule of embodiment 157, the guide RNA of any of embodiments 158-163, the vector of embodiment 164, the cell of embodiment 181, or the system of any of embodiments 165-180, and a pharmaceutical A pharmaceutical composition comprising an acceptable carrier.

183. a) a fusion protein comprising a DNA-binding polypeptide and an adenine deaminase, or a nucleic acid molecule encoding a fusion protein; and

b) a second adenine deaminase having at least 90% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441; or a nucleic acid molecule encoding a deaminase

Composition comprising a.

184. The method of embodiment 183, wherein said second adenine deaminase has at least 90% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441. A composition having

185. The method of embodiment 183, wherein said second adenine deaminase has 100% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 composition.

186. The method of any one of embodiments 183-185, wherein the first adenine deaminase is at least 90 to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 A composition having % sequence identity.

187. The method of any one of embodiments 183-186, wherein the first adenine deaminase is at least 95 to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 A composition having % sequence identity.

188. The method of any one of embodiments 183-186, wherein the first adenine deaminase is 100% to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 A composition having sequence identity.

189. The composition of any one of embodiments 183-188, wherein the DNA-binding polypeptide is a meganuclease, zinc finger fusion protein or TALEN.

190. The composition of any one of embodiments 183-189, wherein the DNA-binding polypeptide is an RNA-guided, DNA-binding polypeptide.

191. The composition of embodiment 190, wherein the RNA-guided, DNA-binding polypeptide is an RNA-guided nuclease (RGN) polypeptide.

192. The composition of embodiment 191, wherein RGN is RGN nickase.

193. A vector comprising a nucleic acid molecule encoding a fusion protein and a nucleic acid molecule encoding a second deaminase, wherein the fusion protein comprises a DNA-binding polypeptide and a first adenine deaminase, and wherein the second adenine deaminase wherein the deaminase has at least 90% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441.

194. The method of embodiment 193, wherein said second adenine deaminase has at least 90% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441. A vector that is to have.

195. The method of embodiment 193, wherein said second adenine deaminase has 100% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 which vector.

196. The method of any one of embodiments 193-195, wherein the first adenine deaminase is at least 90 to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 A vector having % sequence identity.

197. The method of any one of embodiments 193-195, wherein the first adenine deaminase is at least 95 to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 A vector having % sequence identity.

198. The method of any one of embodiments 193-195, wherein the first adenine deaminase is 100% to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 A vector having sequence identity.

199. The vector according to any one of embodiments 193-198, wherein the DNA-binding polypeptide is a meganuclease, zinc finger fusion protein or TALEN.

200. The vector of any one of embodiments 193-198, wherein the DNA-binding polypeptide is an RNA-guided, DNA-binding polypeptide.

201. The vector of embodiment 200, wherein the RNA-guided, DNA-binding polypeptide is an RNA-guided nuclease (RGN) polypeptide.

202. The vector of embodiment 201, wherein RGN is RGN nickase.

203. A cell comprising the vector of any one of embodiments 193-202.

204. a) a fusion protein comprising a DNA-binding polypeptide and a primary adenine deaminase; or nucleic acid molecules encoding fusion proteins; and

b) a second adenine deaminase having at least 90% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441; or a nucleic acid molecule encoding a second adenine deaminase

Cells containing.

205. The method of embodiment 204, wherein said second adenine deaminase has at least 90% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441. cells to have.

206. The method of embodiment 204, wherein said second adenine deaminase has 100% sequence identity to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441. cell that is.

207. The method of any one of embodiments 204-206, wherein the first adenine deaminase is at least 90 to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 A cell having % sequence identity.

208. The method of any one of embodiments 204-206, wherein the first adenine deaminase is at least 95 to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 A cell having % sequence identity.

209. The method of any one of embodiments 204-206, wherein the first adenine deaminase is 100% to any one of SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 A cell having sequence identity.

210. The cell of any one of embodiments 204-209, wherein the DNA-binding polypeptide is a meganuclease, zinc finger fusion protein or TALEN.

211. The cell of any one of embodiments 204-209, wherein the DNA-binding polypeptide is an RNA-guided, DNA-binding polypeptide.

212. The cell of embodiment 211, wherein the RNA-guided, DNA-binding polypeptide is an RNA-guided nuclease (RGN) polypeptide.

213. The cell of embodiment 212, wherein the RGN is an RGN nickase.

214. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the composition of any one of embodiments 183-192, the vector of any one of embodiments 193-202, or the cells of any one of embodiments 203-213.

215. A method of treating a disease comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition of any one of embodiments 69, 100, 142, and 214.

216. The method of embodiment 215, wherein said disease is associated with a causal mutation, and said effective amount of said pharmaceutical composition corrects said causal mutation.

217. The fusion protein of any one of embodiments 14-27, the nucleic acid molecule of any one of embodiments 28-48, the vector of any one of embodiments 49-52 and 193 to 202, for treating a disease in a subject Use of the cell of any one of embodiments 59-63, 135 to 139 and 203 to 213, the system of any one of embodiments 75-99, or the composition of any one of embodiments 183-192.

218. The use according to embodiment 217, wherein said disease is associated with a causative mutation and said treatment comprises correcting said causative mutation.

219. The fusion protein of any one of embodiments 14-27, the nucleic acid molecule of any one of embodiments 28-48, any one of embodiments 49-52 and 193 to 202, for the manufacture of a medicament useful for treating a disease Use of the vector of, the cell of any one of embodiments 59-63, 135 to 139 and 203 to 213, the system of any one of embodiments 75-99, or the composition of any one of embodiments 183-192.

220. The use according to embodiment 219, wherein said disease is associated with a causative mutation and the effective amount of said medicament corrects said causative mutation.

221. A nucleic acid molecule comprising a polynucleotide encoding an RNA-guided nuclease (RGN) polypeptide, wherein said polynucleotide has at least 95% sequence identity to SEQ ID NO: 41 or 60 but SEQ ID NO: a nucleotide sequence encoding an RGN polypeptide comprising an amino acid sequence lacking amino acid residues 590 to 597 of 41 or 60;

Wherein the RGN polypeptide is capable of binding to the target DNA sequence in an RNA-guide sequence specific manner when bound to a guide RNA (gRNA) capable of hybridizing to the target DNA sequence.

nucleic acid molecule.

222. The nucleic acid molecule of embodiment 221, wherein said polynucleotide encoding said RGN polypeptide is operably linked to a promoter heterologous to said polynucleotide.

223. The nucleic acid molecule of embodiment 221 or 222, wherein said RGN polypeptide comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 366 or 368.

224. The nucleic acid molecule of embodiment 221 or 222, wherein said RGN polypeptide comprises the amino acid sequence of SEQ ID NO: 366 or 368.

225. The nucleic acid molecule of any one of embodiments 221-223, wherein said RGN polypeptide is nuclease malfunctioning or functions as a nickase.

226. The nucleic acid molecule of embodiment 225, wherein said nickase has the amino acid sequence set forth in SEQ ID NO: 397 or 398.

227. The nucleic acid molecule of any one of embodiments 221-226, wherein the RGN polypeptide is operably fused to a base-edited polypeptide.

228. A vector comprising the nucleic acid molecule of any one of embodiments 221-227.

229. An isolated polypeptide comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 41 or 60 but lacking amino acid residues 590 to 597 of SEQ ID NO: 41 or 60, wherein the polypeptide is an RNA-guided nuclease. .

230. The isolated polypeptide of embodiment 229, wherein said RGN polypeptide comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 366 or 368.

231. The isolated polypeptide of embodiment 230, wherein said RGN polypeptide comprises the amino acid sequence of SEQ ID NO: 366 or 368.

232. The isolated polypeptide of embodiment 229 or 230, wherein said RGN polypeptide is nuclease malfunctioning or functions as a nickase.

233. The isolated polypeptide of embodiment 232, wherein said nickase has the amino acid sequence set forth in SEQ ID NO: 397 or 398.

234. The isolated polypeptide of any one of embodiments 229-233, wherein the RGN polypeptide is operably fused to a base-edited polypeptide.

235. A cell comprising the nucleic acid molecule of any one of embodiments 221-227, the vector of claim 228, or the polypeptide of any one of embodiments 229-234.

236. An isolated polypeptide comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 407 and having deaminase activity.

237. The isolated polypeptide of embodiment 236, comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 407 and having deaminase activity.

238. The isolated polypeptide of embodiment 236 comprising the amino acid sequence set forth in SEQ ID NO: 407.

239. A nucleic acid molecule comprising a polynucleotide encoding a deaminase polypeptide, wherein the deaminase is:

a) have at least 80% sequence identity to SEQ ID NO: 451, or

b) encoding an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 407

which is encoded by a nucleotide sequence

nucleic acid molecule.

240. The nucleic acid molecule of embodiment 239, wherein the deaminase is encoded by a nucleotide sequence having at least 90% sequence identity to SEQ ID NO:451.

241. The nucleic acid molecule of embodiment 239, wherein the deaminase is encoded by a nucleotide sequence having at least 95% sequence identity to SEQ ID NO:451.

242. The nucleic acid molecule of embodiment 239, wherein the deaminase is encoded by a nucleotide sequence having at least 100% sequence identity to SEQ ID NO:451.

243. The nucleic acid molecule according to any one of embodiments 239-242, further comprising a heterologous promoter operably linked to said polynucleotide.

244. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a polypeptide of any one of embodiments 236-238 or a nucleic acid molecule of any one of embodiments 239-242.

245. A fusion protein comprising a DNA-binding polypeptide and a deaminase having at least 90% sequence identity to SEQ ID NO: 407.

246. The fusion protein of embodiment 245 comprising a DNA-binding polypeptide and a deaminase having at least 95% sequence identity to SEQ ID NO:407.

247. The fusion protein of embodiment 245 comprising a DNA-binding polypeptide and a deaminase having 100% sequence identity to SEQ ID NO:407.

248. The fusion protein of any one of embodiments 245-247, wherein the DNA-binding polypeptide is an RNA-guided nuclease (RGN) polypeptide.

249. The fusion protein of embodiment 248, wherein the RGN polypeptide is a Type II CRISPR-Cas polypeptide or a Type V CRISPR-Cas polypeptide.

250. The method according to any one of embodiments 248-249, wherein the RGN polypeptide is Cas9, CasX, CasY, Cpf1, C2c1, C2c2, C2c3, GeoCas9, CjCas9, Cas12a, Cas12b, Cas12g, Cas12h, Cas12i, Cas13b, Cas13c, Cas13d, Cas14, Csn2, xCas9, SpCas9-NG, LbCas12a, AsCas12a, Cas9-KKH, circular permutation Cas9, Argonaut (Ago), SmacCas9, Spy-macCas9 domain, or SEQ ID NO: 41, 60, 366 or 368 A fusion protein that is an RGN polypeptide having the amino acid sequence shown.

251. The fusion protein of any one of embodiments 248-250, wherein the RGN polypeptide is a nickase.

252. The fusion protein of embodiment 251, wherein the nickase has an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398.

253. The fusion protein of embodiment 251, wherein the nickase has an amino acid sequence with 100% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398.

254. A nucleic acid molecule comprising a polynucleotide encoding a DNA-binding polypeptide and a fusion protein comprising a deaminase, wherein the deaminase:

a) have at least 80% sequence identity to SEQ ID NO: 451, or

b) encoding an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 407

which is encoded by a nucleotide sequence

nucleic acid molecule.

255. The nucleic acid molecule of embodiment 254, wherein the deaminase is encoded by a nucleotide sequence having at least 90% sequence identity to SEQ ID NO:451.

256. The nucleic acid molecule of embodiment 254, wherein the deaminase is encoded by a nucleotide sequence having at least 95% sequence identity to SEQ ID NO:451.

257. The nucleic acid molecule of embodiment 254, wherein the deaminase is encoded by a nucleotide sequence having at least 100% sequence identity to SEQ ID NO:451.

258. The nucleic acid molecule of any one of embodiments 254-257, wherein the DNA-binding polypeptide is an RGN polypeptide.

259. The nucleic acid molecule of embodiment 258, wherein the RGN is a Type II CRISPR-Cas polypeptide or a Type V CRISPR-Cas polypeptide.

260. The method of any one of embodiments 258-259, wherein the RGN polypeptide is Cas9, CasX, CasY, Cpf1, C2c1, C2c2, C2c3, GeoCas9, CjCas9, Cas12a, Cas12b, Cas12g, Cas12h, Cas12i, Cas13b, Cas13c, Cas13d, Cas14, Csn2, xCas9, SpCas9-NG, LbCas12a, AsCas12a, Cas9-KKH, circular permutation Cas9, Argonaut (Ago), SmacCas9, Spy-macCas9 domain, or any one of SEQ ID NOs: 41, 60, 366, or 368 A nucleic acid molecule that is an RGN polypeptide having the amino acid sequence set forth in.

261. The nucleic acid molecule of any one of embodiments 258-260, wherein the RGN polypeptide is a nickase.

262. The nucleic acid molecule of embodiment 261, wherein the nickase has an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398.

263. The nucleic acid molecule of embodiment 262, wherein the nickase has an amino acid sequence with 100% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398.

264. A vector comprising the nucleic acid molecule of any one of embodiments 254-263.

265. The vector of embodiment 264, further comprising at least one nucleotide sequence encoding a guide RNA (gRNA) capable of hybridizing to the target sequence.

266. A ribonucleoprotein (RNP) complex comprising the fusion protein of any one of embodiments 245-253 and a guide RNA linked to the DNA-binding polypeptide of the fusion protein.

267. A cell comprising the fusion protein of any one of embodiments 245-253, the nucleic acid molecule of any one of embodiments 254-263, the vector of any one of embodiments 264-265, or the RNP complex of embodiment 266.

268. A system for modifying a target DNA molecule comprising a target DNA sequence,

The system

a) a fusion protein comprising an RNA-guided nuclease (RGN) polypeptide and a deaminase, wherein the deaminase has an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 407, or a nucleotide sequence encoding the fusion protein; and

b) one or more guide RNAs capable of hybridizing to the target DNA sequence, or one or more nucleotide sequences encoding one or more guide RNAs (gRNAs)

contains;

Wherein the one or more guide RNAs are capable of forming a complex with the fusion protein to direct the fusion protein to bind to the target DNA sequence and modify the target DNA molecule.

system.

269. The system of embodiment 268, wherein said deaminase has an amino acid sequence with at least 95% sequence identity to SEQ ID NO:407.

270. The system of embodiment 268, wherein said deaminase has an amino acid sequence with 100% sequence identity to SEQ ID NO:407.

271. The system according to any one of embodiments 268-270, wherein at least one of the nucleotide sequence encoding the one or more guide RNAs and the nucleotide sequence encoding the fusion protein is operably linked to a promoter heterologous to the nucleotide sequence. .

272. The system according to any one of embodiments 268-271, wherein the target DNA sequence is located adjacent to a protospacer adjacent motif (PAM) recognized by the RGN polypeptide.

273. The method of any one of embodiments 268-272, wherein the target DNA sequence consists of SEQ ID NOs: 62-97, 116-139, 152-185, 203-234, 251-286, 305-344, 562 and 563 A system comprising a nucleic acid sequence selected from the group, or the complement thereof.

274. The method of any one of embodiments 268-273, wherein the gRNA sequence is selected from the group consisting of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564 A system comprising a nucleic acid sequence.

275. The system of any one of embodiments 268-274, wherein the RGN polypeptide of the fusion protein is a Type II CRISPR-Cas polypeptide or a Type V CRISPR-Cas polypeptide.

276. The method according to any one of embodiments 272-275, wherein the RGN polypeptide is Cas9, CasX, CasY, Cpf1, C2c1, C2c2, C2c3, GeoCas9, CjCas9, Cas12a, Cas12b, Cas12g, Cas12h, Cas12i, Cas13b, Cas13c, Cas13d, Cas14, Csn2, xCas9, SpCas9-NG, LbCas12a, AsCas12a, Cas9-KKH, circular permutation Cas9, Argonaut (Ago), SmacCas9, Spy-macCas9 domain, or SEQ ID NO: 41, 60, 366 or 368 A system that is an RGN having the amino acid sequence shown.

277. The system of embodiment 276, wherein the RGN polypeptide is a nickcase.

278. The system of embodiment 277, wherein the nickase has an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398.

279. A pharmaceutically acceptable carrier and the fusion protein of any one of embodiments 245-253, the nucleic acid molecule of any one of embodiments 254-263, the vector of any one of embodiments 264-265, the RNP complex of embodiment 266, A pharmaceutical composition comprising the cell of embodiment 267, or the system of any one of embodiments 268-28.

280. A method of modifying a target DNA molecule comprising a target sequence, comprising:

a) under conditions suitable for the formation of an RNA-guided nuclease polypeptide (RGN)-deaminase ribonucleotide complex

i) one or more guide RNAs capable of hybridizing to a target DNA sequence; and

ii) a fusion protein comprising RGN and at least one deaminase, wherein the deaminase has an amino acid sequence having at least 90% sequence identity to SEQ ID NO:407.

assembling an RGN-deaminase ribonucleotide complex by combining; and

b) contacting the target DNA molecule or a cell containing the target DNA molecule with the assembled RGN-deaminase ribonucleotide complex

contains;

wherein the one or more guide RNAs hybridize to the target DNA sequence, thereby directing the fusion protein to bind to the target DNA sequence, and modification of the target DNA molecule occurs.

method.

281. The method of embodiment 280, wherein the target DNA sequence is a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 62-97, 116-139, 152-185, 203-234, 251-286, 305-344, 562 and 563 , or a method comprising its complement.

282. The method of any one of embodiments 280-281, wherein the gRNA sequence is selected from the group consisting of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564 A method comprising a nucleic acid sequence.

283. The method according to any one of embodiments 280-283, performed in vitro, in vivo or ex vivo.

284. A method of treating a subject having or at risk of developing a disease, disorder or condition comprising:

The above method

To a subject comprising the fusion protein of any one of embodiments 245-253, the nucleic acid molecule of any one of embodiments 254-263, the vector of any one of embodiments 264-265, the RNP complex of embodiment 266, the cell of embodiment 267, Administering the system of any one of embodiments 268-28, or the pharmaceutical composition of embodiment 279

which includes

method.

285. Any of the gRNAs of embodiment 284 comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564 A method further comprising administering one.

286. An isolated polypeptide comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 405 and having deaminase activity.

287. The isolated polypeptide of embodiment 286, comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 405 and having deaminase activity.

288. The isolated polypeptide of embodiment 286 comprising the amino acid sequence set forth in SEQ ID NO: 407.

289. A nucleic acid molecule comprising a polynucleotide encoding a deaminase polypeptide, wherein the deaminase is:

a) has at least 80% sequence identity to SEQ ID NO: 449, or

b) encoding an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 405

which is encoded by a nucleotide sequence

nucleic acid molecule.

290. The nucleic acid molecule of embodiment 289, wherein the deaminase is encoded by a nucleotide sequence having at least 90% sequence identity to SEQ ID NO:449.

291. The nucleic acid molecule of embodiment 289, wherein the deaminase is encoded by a nucleotide sequence having at least 95% sequence identity to SEQ ID NO:449.

292. The nucleic acid molecule of embodiment 289, wherein the deaminase is encoded by a nucleotide sequence having at least 100% sequence identity to SEQ ID NO:449.

293. The nucleic acid molecule according to any one of embodiments 289-292, further comprising a heterologous promoter operably linked to said polynucleotide.

294. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a polypeptide of any one of embodiments 286-288 or a nucleic acid molecule of any one of embodiments 289-293.

295. A fusion protein comprising a DNA-binding polypeptide and a deaminase having at least 90% sequence identity to SEQ ID NO: 405.

296. The fusion protein of embodiment 295 comprising a DNA-binding polypeptide and a deaminase having at least 95% sequence identity to SEQ ID NO:405.

297. The fusion protein of embodiment 295 comprising a DNA-binding polypeptide and a deaminase having 100% sequence identity to SEQ ID NO:405.

298. The fusion protein of any one of embodiments 295-297, wherein the DNA-binding polypeptide is an RNA-guided nuclease (RGN) polypeptide.

299. The fusion protein of embodiment 298, wherein the RGN polypeptide is a Type II CRISPR-Cas polypeptide or a Type V CRISPR-Cas polypeptide.

300. The method of any one of embodiments 298-299, wherein the RGN polypeptide is Cas9, CasX, CasY, Cpf1, C2c1, C2c2, C2c3, GeoCas9, CjCas9, Cas12a, Cas12b, Cas12g, Cas12h, Cas12i, Cas13b, Cas13c, Cas13d, Cas14, Csn2, xCas9, SpCas9-NG, LbCas12a, AsCas12a, Cas9-KKH, circular permutation Cas9, Argonaut (Ago), SmacCas9, Spy-macCas9 domain, or SEQ ID NO: 41, 60, 366 or 368 A fusion protein that is an RGN polypeptide having the amino acid sequence shown.

301. The fusion protein of any one of embodiments 298-300, wherein the RGN polypeptide is a nickase.

302. The fusion protein of embodiment 301, wherein the nickase has an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398.

303. The fusion protein of embodiment 301, wherein the nickase has an amino acid sequence with 100% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398.

304. A nucleic acid molecule comprising a polynucleotide encoding a DNA-binding polypeptide and a fusion protein comprising a deaminase, wherein the deaminase:

a) has at least 80% sequence identity to SEQ ID NO: 449, or

b) encoding an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 405

which is encoded by a nucleotide sequence

nucleic acid molecule.

305. The nucleic acid molecule of embodiment 304, wherein the deaminase is encoded by a nucleotide sequence having at least 90% sequence identity to SEQ ID NO:449.

306. The nucleic acid molecule of embodiment 304, wherein the deaminase is encoded by a nucleotide sequence having at least 95% sequence identity to SEQ ID NO:449.

307. The nucleic acid molecule of embodiment 304, wherein the deaminase is encoded by a nucleotide sequence having at least 100% sequence identity to SEQ ID NO:449.

308. The nucleic acid molecule of any one of embodiments 304-307, wherein the DNA-binding polypeptide is an RGN polypeptide.

309. The nucleic acid molecule of embodiment 308, wherein the RGN is a Type II CRISPR-Cas polypeptide or a Type V CRISPR-Cas polypeptide.

310. The method of any one of embodiments 308-309, wherein the RGN polypeptide is Cas9, CasX, CasY, Cpf1, C2c1, C2c2, C2c3, GeoCas9, CjCas9, Cas12a, Cas12b, Cas12g, Cas12h, Cas12i, Cas13b, Cas13c, Cas13d, Cas14, Csn2, xCas9, SpCas9-NG, LbCas12a, AsCas12a, Cas9-KKH, circular permutation Cas9, Argonaut (Ago), SmacCas9, Spy-macCas9 domain, or any one of SEQ ID NOs: 41, 60, 366, or 368 A nucleic acid molecule that is an RGN polypeptide having the amino acid sequence set forth in.

311. The nucleic acid molecule of any one of embodiments 308-310, wherein the RGN polypeptide is a nickase.

312. The nucleic acid molecule of embodiment 311, wherein the nickase has an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398.

313. The nucleic acid molecule of embodiment 312, wherein the nickase has an amino acid sequence with 100% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398.

314. A vector comprising the nucleic acid molecule of any one of embodiments 304-313.

315. The vector of embodiment 314, further comprising at least one nucleotide sequence encoding a guide RNA (gRNA) capable of hybridizing to the target sequence.

316. A ribonucleoprotein (RNP) complex comprising the fusion protein of any one of embodiments 295-303 and a guide RNA linked to the DNA-binding polypeptide of the fusion protein.

317. A cell comprising the fusion protein of any one of embodiments 295-303, the nucleic acid molecule of any one of embodiments 304-313, the vector of any one of embodiments 314-315, or the RNP complex of embodiment 316.

318. A system for modifying a target DNA molecule comprising a target DNA sequence, comprising:

The system

a) a fusion protein comprising an RNA-guided nuclease (RGN) polypeptide and a deaminase, wherein the deaminase has an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 405, or a nucleotide sequence encoding the fusion protein; and

b) one or more guide RNAs capable of hybridizing to the target DNA sequence, or one or more nucleotide sequences encoding one or more guide RNAs (gRNAs)

contains;

Wherein the one or more guide RNAs are capable of forming a complex with the fusion protein to direct the fusion protein to bind to the target DNA sequence and modify the target DNA molecule.

system.

319. The system of embodiment 318, wherein said deaminase has an amino acid sequence with at least 95% sequence identity to SEQ ID NO:405.

320. The system of embodiment 318, wherein said deaminase has an amino acid sequence with 100% sequence identity to SEQ ID NO:405.

321. The system of any one of embodiments 318-320, wherein at least one of the nucleotide sequence encoding the one or more guide RNAs and the nucleotide sequence encoding the fusion protein is operably linked to a promoter heterologous to the nucleotide sequence. .

322. The system of any one of embodiments 318-321, wherein the target DNA sequence is located adjacent to a protospacer adjacent motif (PAM) recognized by the RGN polypeptide.

323. The method of any one of embodiments 318-322, wherein the target DNA sequence consists of SEQ ID NOs: 62-97, 116-139, 152-185, 203-234, 251-286, 305-344, 562 and 563 A system comprising a nucleic acid sequence selected from the group, or the complement thereof.

324. The method of any one of embodiments 318-323, wherein the gRNA sequence is selected from the group consisting of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564 A system comprising a nucleic acid sequence.

325. The system of any one of embodiments 318-324, wherein the RGN polypeptide of the fusion protein is a Type II CRISPR-Cas polypeptide or a Type V CRISPR-Cas polypeptide.

326. The method according to any one of embodiments 322-325, wherein the RGN polypeptide is Cas9, CasX, CasY, Cpf1, C2c1, C2c2, C2c3, GeoCas9, CjCas9, Cas12a, Cas12b, Cas12g, Cas12h, Cas12i, Cas13b, Cas13c, Cas13d, Cas14, Csn2, xCas9, SpCas9-NG, LbCas12a, AsCas12a, Cas9-KKH, circular permutation Cas9, Argonaut (Ago), SmacCas9, Spy-macCas9 domain, or SEQ ID NO: 41, 60, 366 or 368 A system that is an RGN having the amino acid sequence shown.

327. The system of embodiment 326, wherein the RGN polypeptide is a nickcase.

328. The system of embodiment 327, wherein the nickase has an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398.

329. A pharmaceutically acceptable carrier and the fusion protein of any one of embodiments 295-303, the nucleic acid molecule of any one of embodiments 304-313, the vector of any one of embodiments 314-315, the RNP complex of embodiment 316, A pharmaceutical composition comprising the cell of embodiment 317, or the system of any one of embodiments 318-328.

330. A method of modifying a target DNA molecule comprising a target sequence, comprising:

a) under conditions suitable for the formation of an RNA-guided nuclease polypeptide (RGN)-deaminase ribonucleotide complex

i) one or more guide RNAs capable of hybridizing to a target DNA sequence; and

ii) a fusion protein comprising RGN and at least one deaminase, wherein the deaminase has an amino acid sequence having at least 90% sequence identity to SEQ ID NO:405.

assembling an RGN-deaminase ribonucleotide complex by combining; and

b) contacting the target DNA molecule or a cell containing the target DNA molecule with the assembled RGN-deaminase ribonucleotide complex

contains;

wherein the one or more guide RNAs hybridize to the target DNA sequence, thereby directing the fusion protein to bind to the target DNA sequence, and modification of the target DNA molecule occurs.

method.

331. The method of embodiment 330, wherein the target DNA sequence is a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 62-97, 116-139, 152-185, 203-234, 251-286, 305-344, 562 and 563 , or a method comprising its complement.

332. The method of any one of embodiments 330-331, wherein the gRNA sequence is selected from the group consisting of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564 A method comprising a nucleic acid sequence.

333. The method according to any one of embodiments 330-332, performed in vitro, in vivo or ex vivo.

334. A method of treating a subject having or at risk of developing a disease, disorder or condition comprising:

The above method

Subjecting the subject to the fusion protein of any one of embodiments 295-303, the nucleic acid molecule of any one of embodiments 304-313, the vector of any one of embodiments 314-315, the RNP complex of embodiment 316, the cell of embodiment 317, Administering the system of any one of embodiments 318-328, or the pharmaceutical composition of embodiment 329

which includes

method.

335. Any of the gRNAs of embodiment 334 comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564 A method further comprising administering one.

336. An isolated polypeptide comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 399 and having deaminase activity.

337. The isolated polypeptide of embodiment 336, comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 399 and having deaminase activity.

338. The isolated polypeptide of embodiment 336 comprising the amino acid sequence set forth in SEQ ID NO: 399.

339. A nucleic acid molecule comprising a polynucleotide encoding a deaminase polypeptide, wherein the deaminase is:

a) have at least 80% sequence identity to SEQ ID NO: 443, or

b) encoding an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 399

which is encoded by a nucleotide sequence

nucleic acid molecule.

340. The nucleic acid molecule of embodiment 339, wherein the deaminase is encoded by a nucleotide sequence having at least 90% sequence identity to SEQ ID NO:443.

341. The nucleic acid molecule of embodiment 339, wherein the deaminase is encoded by a nucleotide sequence having at least 95% sequence identity to SEQ ID NO:443.

342. The nucleic acid molecule of embodiment 339, wherein the deaminase is encoded by a nucleotide sequence having at least 100% sequence identity to SEQ ID NO:443.

343. The nucleic acid molecule according to any one of embodiments 339-342, further comprising a heterologous promoter operably linked to said polynucleotide.

344. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a polypeptide of any one of embodiments 336-338 or a nucleic acid molecule of any one of embodiments 339-342.

345. A fusion protein comprising a DNA-binding polypeptide and a deaminase having at least 90% sequence identity to SEQ ID NO: 399.

346. The fusion protein of embodiment 345 comprising a DNA-binding polypeptide and a deaminase having at least 95% sequence identity to SEQ ID NO: 399.

347. The fusion protein of embodiment 345 comprising a DNA-binding polypeptide and a deaminase having 100% sequence identity to SEQ ID NO: 399.

348. The fusion protein of any one of embodiments 345-347, wherein the DNA-binding polypeptide is an RNA-guided nuclease (RGN) polypeptide.

349. The fusion protein of embodiment 348, wherein the RGN polypeptide is a Type II CRISPR-Cas polypeptide or a Type V CRISPR-Cas polypeptide.

350. The method according to any one of embodiments 348-349, wherein the RGN polypeptide is Cas9, CasX, CasY, Cpf1, C2c1, C2c2, C2c3, GeoCas9, CjCas9, Cas12a, Cas12b, Cas12g, Cas12h, Cas12i, Cas13b, Cas13c, Cas13d, Cas14, Csn2, xCas9, SpCas9-NG, LbCas12a, AsCas12a, Cas9-KKH, circular permutation Cas9, Argonaut (Ago), SmacCas9, Spy-macCas9 domain, or any one of SEQ ID NOs: 41, 60, 366, or 368 A fusion protein that is an RGN polypeptide having the amino acid sequence set forth in.

351. The fusion protein of any one of embodiments 348-350, wherein the RGN polypeptide is a nickase.

352. The fusion protein of embodiment 351, wherein the nickase has an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398.

353. The fusion protein of embodiment 351, wherein the nickase has an amino acid sequence with 100% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398.

354. A nucleic acid molecule comprising a polynucleotide encoding a DNA-binding polypeptide and a fusion protein comprising a deaminase, wherein the deaminase:

a) have at least 80% sequence identity to SEQ ID NO: 443, or

b) encoding an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 399

which is encoded by a nucleotide sequence

nucleic acid molecule.

355. The nucleic acid molecule of embodiment 354, wherein the deaminase is encoded by a nucleotide sequence having at least 90% sequence identity to SEQ ID NO:443.

356. The nucleic acid molecule of embodiment 354, wherein the deaminase is encoded by a nucleotide sequence having at least 95% sequence identity to SEQ ID NO:443.

357. The nucleic acid molecule of embodiment 354, wherein the deaminase is encoded by a nucleotide sequence having at least 100% sequence identity to SEQ ID NO:443.

358. The nucleic acid molecule of any one of embodiments 354-357, wherein the DNA-binding polypeptide is an RGN polypeptide.

359. The nucleic acid molecule of embodiment 358, wherein the RGN is a Type II CRISPR-Cas polypeptide or a Type V CRISPR-Cas polypeptide.

360. The method of any one of embodiments 358-359, wherein the RGN polypeptide is Cas9, CasX, CasY, Cpf1, C2c1, C2c2, C2c3, GeoCas9, CjCas9, Cas12a, Cas12b, Cas12g, Cas12h, Cas12i, Cas13b, Cas13c, Cas13d, Cas14, Csn2, xCas9, SpCas9-NG, LbCas12a, AsCas12a, Cas9-KKH, circular permutation Cas9, Argonaut (Ago), SmacCas9, Spy-macCas9 domain, or any one of SEQ ID NOs: 41, 60, 366, or 368 A nucleic acid molecule that is an RGN polypeptide having the amino acid sequence set forth in.

361. The nucleic acid molecule of any one of embodiments 358-360, wherein the RGN polypeptide is a nickase.

362. The nucleic acid molecule of embodiment 361, wherein the nickase has an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398.

363. The nucleic acid molecule of embodiment 362, wherein the nickase has an amino acid sequence with 100% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398.

364. A vector comprising the nucleic acid molecule of any one of embodiments 354-363.

365. The vector of embodiment 364, further comprising at least one nucleotide sequence encoding a guide RNA (gRNA) capable of hybridizing to the target sequence.

366. A ribonucleoprotein (RNP) complex comprising the fusion protein of any one of embodiments 345-353 and a guide RNA linked to the DNA-binding polypeptide of the fusion protein.

367. A cell comprising the fusion protein of any one of embodiments 345-353, the nucleic acid molecule of any one of embodiments 354-363, the vector of any one of embodiments 364-365, or the RNP complex of embodiment 366.

368. A system for modifying a target DNA molecule comprising a target DNA sequence, comprising:

The system

a) a fusion protein comprising an RNA-guided nuclease (RGN) polypeptide and a deaminase, wherein the deaminase has an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 399, or a nucleotide sequence encoding the fusion protein; and

b) one or more guide RNAs capable of hybridizing to the target DNA sequence, or one or more nucleotide sequences encoding one or more guide RNAs (gRNAs)

contains;

Wherein the one or more guide RNAs are capable of forming a complex with the fusion protein to direct the fusion protein to bind to the target DNA sequence and modify the target DNA molecule.

system.

369. The system of embodiment 368, wherein said deaminase has an amino acid sequence with at least 95% sequence identity to SEQ ID NO:399.

370. The system of embodiment 368, wherein said deaminase has an amino acid sequence with 100% sequence identity to SEQ ID NO:399.

371. The system of any one of embodiments 368-370, wherein at least one of the nucleotide sequence encoding the one or more guide RNAs and the nucleotide sequence encoding the fusion protein is operably linked to a promoter heterologous to the nucleotide sequence. .

372. The system of any one of embodiments 368-371, wherein the target DNA sequence is located adjacent to a protospacer adjacent motif (PAM) recognized by the RGN polypeptide.

373. The method of any one of embodiments 368-372, wherein the target DNA sequence consists of SEQ ID NOs: 62-97, 116-139, 152-185, 203-234, 251-286, 305-344, 562 and 563 A system comprising a nucleic acid sequence selected from the group, or the complement thereof.

374. The method of any one of embodiments 368-373, wherein the gRNA sequence is selected from the group consisting of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564 A system comprising a nucleic acid sequence.

375. The system of any one of embodiments 368-374, wherein the RGN polypeptide of the fusion protein is a Type II CRISPR-Cas polypeptide or a Type V CRISPR-Cas polypeptide.

376. The method of any one of embodiments 372-375, wherein the RGN polypeptide is Cas9, CasX, CasY, Cpf1, C2c1, C2c2, C2c3, GeoCas9, CjCas9, Cas12a, Cas12b, Cas12g, Cas12h, Cas12i, Cas13b, Cas13c, Cas13d, Cas14, Csn2, xCas9, SpCas9-NG, LbCas12a, AsCas12a, Cas9-KKH, circular permutation Cas9, Argonaut (Ago), SmacCas9, Spy-macCas9 domain, or SEQ ID NO: 41, 60, 366 or 368 A system that is an RGN having the amino acid sequence shown.

377. The system of embodiment 376, wherein the RGN polypeptide is a nickcase.

378. The system of embodiment 377, wherein the nickase has an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398.

379. A pharmaceutically acceptable carrier and the fusion protein of any one of embodiments 345-353, the nucleic acid molecule of any one of embodiments 354-363, the vector of any one of embodiments 364-365, the RNP complex of any one of embodiment 366, A pharmaceutical composition comprising the cell of embodiment 367, or the system of any one of embodiments 368-378.

380. A method of modifying a target DNA molecule comprising a target sequence, comprising:

a) under conditions suitable for the formation of an RNA-guided nuclease polypeptide (RGN)-deaminase ribonucleotide complex

i) one or more guide RNAs capable of hybridizing to a target DNA sequence; and

ii) a fusion protein comprising RGN and at least one deaminase, wherein the deaminase has an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 399

assembling an RGN-deaminase ribonucleotide complex by combining; and

b) contacting the target DNA molecule or a cell containing the target DNA molecule with the assembled RGN-deaminase ribonucleotide complex

contains;

wherein the one or more guide RNAs hybridize to the target DNA sequence, thereby directing the fusion protein to bind to the target DNA sequence, and modification of the target DNA molecule occurs.

method.

381. The method of embodiment 380, wherein the target DNA sequence is a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 62-97, 116-139, 152-185, 203-234, 251-286, 305-344, 562 and 563 , or a method comprising its complement.

382. The method of any one of embodiments 380-381, wherein the gRNA sequence is selected from the group consisting of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564 A method comprising a nucleic acid sequence.

383. The method according to any one of embodiments 380-382, performed in vitro, in vivo or ex vivo.

384. A method of treating a subject having or at risk of developing a disease, disorder or condition comprising:

The above method

Subjecting the subject to the fusion protein of any one of embodiments 345-353, the nucleic acid molecule of any one of embodiments 354-363, the vector of any one of embodiments 364-365, the RNP complex of embodiment 366, the cell of embodiment 367, Administering the system of any one of embodiments 368-378, or the pharmaceutical composition of embodiment 379

which includes

method.

385. Any of the gRNAs of embodiment 384 comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564 A method further comprising administering one.

386. A method of treating or reducing at least one symptom of cystic fibrosis, comprising:

The method can be used to administer an effective amount to a subject in need thereof.

a) an RNA-guided nuclease polypeptide (RGN) and a deaminase, wherein the deaminase is SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 A fusion protein having an amino acid sequence having at least 90% sequence identity to any one of, or a polynucleotide encoding the fusion protein, wherein the polynucleotide encoding the fusion protein is capable of expressing the fusion protein in a cell. a polynucleotide operably linked to a promoter that allows; and

b) at least one guide RNA (gRNA) capable of hybridizing to a target DNA sequence, or a polynucleotide encoding said gRNA, wherein said polynucleotide encoding a gRNA is operable to a promoter enabling expression of the gRNA in a cell. Polynucleotides that are closely linked

Including introducing a;

Whereby the fusion protein and gRNA target the genomic location of the causative mutation and modify the genomic sequence to remove the causative mutation.

method.

387. The method of embodiment 386, wherein the gRNA is any one of SEQ ID NOs: 62-97, 116-139, 152-185, 203-234, 251-286, 305-344, 562 and 563, or the complement thereof A method comprising a targeting spacer sequence.

388. The method of embodiment 386 or 387, wherein the gRNA comprises any one of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564 .

389. The method of any one of embodiments 386-388, wherein said RGN has an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 41, 60, 366 and 368.

390. The method of any one of embodiments 386-389, wherein said RGN has an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398 .

The following examples are provided by way of illustration and without limitation.

<Experiment>

Example 1: Demonstration of Base Editing in Mammalian Cells

The deaminase shown in Table 1 below was produced based on naturally occurring deaminase, which was then mutated and selected for adenine deaminase activity in prokaryotic cells.

Table 1: Deaminase sequences

To determine whether the deaminase of Table 1 can perform adenine base editing in mammalian cells, each deaminase was operably fused to RGN nickase to produce a fusion protein. A residue predicted to inactivate the RuvC domain of RGN APG07433.1 (represented as SEQ ID NO: 41; described in PCT Publication WO 2019/236566, incorporated herein by reference) was identified and RGN was converted into a nickase variant (nAPG07433.1; SEQ ID NO: 42). Nickase variants of RGN are referred to herein as "nRGN". It should be understood that any nickase variant of RGN can be used to produce the fusion proteins of the present invention.

For mammalian expression, the codon-optimized deaminase and nRGN nucleotide sequences were synthesized as fusion proteins with an N-terminal nuclear localization tag and cloned into a pTwist CMV (Twist Biosciences) expression plasmid. Each fusion protein has, starting at the amino terminus, a SV40 NLS (SEQ ID NO: 43), a 3X FLAG tag (SEQ ID NO: 44) operably linked to its C-terminal end, operable at its C-terminal end a deaminase operably linked to its C-terminal end, a peptide linker operably linked to its C-terminal end (SEQ ID NO: 45), nRGN operably linked to its C-terminal end (eg, nAPG07433 with SEQ ID NO: 42. 1), and finally a nucleoplasmin NLS (SEQ ID NO: 45) operably linked to its C-terminal end. All fusion proteins contain at least one NLS and 3X FLAG tag as described above.

An expression plasmid containing an expression cassette encoding an sgRNA expressed by the human U6 promoter (SEQ ID NO: 50) was also produced. Table 2 shows human genome target sequences and sgRNA sequences for guiding fusion proteins to genome targets.

Table 2: Guide RNA sequences

500 ng of a plasmid containing an expression cassette containing the coding sequence for the fusion protein for each deaminase listed in Table 1 and 500 ng of a plasmid containing an expression cassette encoding the sgRNA shown in Table 2 were lipofected. It was co-transfected into HEK293FT cells at 75-90% confluency in 24-well plates using Tamin 2000 reagent (Life Technologies). Cells were then incubated at 37° C. for 72 hours. After incubation, genomic DNA was then extracted using NucleoSpin 96 tissue (Macherey-Nagel) according to the manufacturer's protocol. The genomic region flanking the targeted genomic site was PCR amplified using the primers in Table 2, and the product was purified using the ZR-96 DNA Clean and Concentrator (Zimo Research) according to the manufacturer's protocol. did Purified PCR products were subjected to next-generation sequencing on an Illumina MiSeq. Typically, 100,000 250 bp paired-end reads (2 x 100,000 reads) are generated per amplicon. Reads were analyzed using CRISPResso (Pinello, et al. 2016 Nature Biotech, 34:695-697) to calculate edit rates. Output alignments were analyzed for INDEL formation or introduction of specific adenine mutations. Tables 3-7 show adenine base editing for each fusion protein comprising nAPG07433.1 and the deaminase from Table 1 and the guide RNA from Table 2. The deaminase component of each fusion protein is indicated. Editing rates for adenine in or close to the target sequence are indicated. “A5” represents, for example, an adenine at position 5 of the target sequence. The position of each nucleotide in the target sequence was determined by numbering the first nucleotide in the target sequence closest to the PAM as position 1, with position numbers increasing in the 3' direction from the PAM sequence. The table also indicates which nucleotides the adenine was changed to, and at what rate. For example, Table 3 shows that in the case of the APG09982-nAPG07433.1 fusion protein, adenine at position 13 was mutated to guanine at a rate of 1.2%.

Table 3: A>N edit rate using guide SGN000139

All fusion proteins showed detectable A>G transitions at positions A12 and A13. APG09982 and APG06333 showed at least 1% editing at position A13.

Table 4: A>N edit rate using guide SGN000143

All fusion proteins showed A>G transitions at positions A11 and A14. APG09982 showed 4.5% conversion of A11 to G and 1.7% conversion of A14 to G.

Table 5: A>N edit rate using guide SGN000186

All fusion proteins showed >1% base editing at multiple positions within target SGN000186. APG09102 exhibited greater than 6.2% A>G conversion at position A16; It also showed >2% base editing at positions A9 and A18. For all fusion proteins tested, position A16 was most highly edited.

Table 6: A>N edit rate using guide SGN000194

For SGN00194, all fusion proteins showed 0.9%-1.8% A>G editing at position A15. No detectable editing was seen at positions A21, A23, A26 and A27.

Table 7: A>N edit rate using guide SGN000930

A14 was the most highly edited position in SGN000930 with all fusion proteins tested. Editing rates ranged from 0.3%-1.2% for A>G conversions.

Example 2: Fluorescence Assay for Targeted Adenine Base Editing

Enhancement containing the W58X mutation that causes a premature stop codon so that the W58 codon can be reverted from the stop codon (TGA) to the wild-type tryptophan (TGG) residue using adenine deaminase to change position 3 to G A vector (GFP-STOP, SEQ ID NO: 47) was constructed containing the modified green fluorescent protein (EGFP). Successful A to G conversion results in quantifiable expression of EGFP. A second vector (SEQ ID NO: 48) capable of expressing a guide RNA targeting the deaminase-RGN fusion protein to the region around the W58X mutation was also produced.

This GFP-STOP reporter vector was transfected into HEK293T cells using lipofection or electroporation together with a vector capable of expressing the deaminase-nRGN fusion protein and the corresponding guide RNA. For lipofection, cells were seeded at 1x10 ⁵ cells/well in 24-well plates the day before transfection in growth medium (DMEM + 10% fetal bovine serum + 1% penicillin/streptomycin). 500 ng each of GFP-STOP reporter vector, deaminase-RGN expression vector, and guide RNA expression vector were transfected using Lipofectamine® 3000 reagent (Thermo Fisher Scientific) according to the manufacturer's instructions . For electroporation, cells were electroporated using the Neon® Transfection System (Thermo Fisher Scientific) according to the manufacturer's instructions.

In addition to transient transfection of a fluorescent GFP-STOP reporter, a stable cell line carrying a chromosomally integrated GFP-STOP cassette was generated. Once stable cell lines were established, for transfection, cells were seeded at 1x10 ⁵ cells/well in 24-well plates the day before transfection in growth medium (DMEM + 10% fetal bovine serum + 1% penicillin/streptomycin). 500 ng of each deaminase-nRGN expression vector and guide RNA expression vector were transfected using Lipofectamine® 3000 reagent (Thermo Fisher Scientific) according to the manufacturer's instructions. For electroporation, cells were electroporated using the Neon® Transfection System (Thermo Fisher Scientific) according to the manufacturer's instructions.

24-48 hours after lipofection or electroporation, expression of GFP was determined by microscopically examining the cells for the presence of GFP+ cells. After visual inspection, the ratio of GFP+ cells to GFP− cells can be determined. Fluorescence was observed in mammalian cells expressing each deaminase-nRGN fusion protein, indicating that the fusion protein was successfully targeted to the GFP-STOP mutation and the mutation was edited to restore the fluorescence of the GFP protein.

After microscopic analysis, cells were lysed in RIPA buffer and the resulting lysate was analyzed on a fluorescence plate reader to determine the fluorescence intensity of GFP (Table 8). One skilled in the art will understand that cells can be analyzed by flow cytometry or fluorescence activated cell sorting to determine the exact proportion of GFP+ and GFP− cells.

Table 8: GFP-STOP assay results

N.D = not detected; + = few GFP+ cells detected; ++ = few GFP+ cells detected; +++ = many GFP+ cells detected

Example 3: Demonstration of Base Editing in Mammalian Cells

The deaminase shown in Table 9 below was produced based on naturally occurring deaminase, which was then mutated and selected for adenine deaminase activity in prokaryotic cells.

Table 9: Deaminase sequences

To determine if the deaminase of Table 9 can perform adenine base editing in mammalian cells, each deaminase was operably fused to RGN nickase to produce a fusion protein. A residue predicted to inactivate the RuvC domain of RGN APG07433.1 (represented as SEQ ID NO: 41; described in PCT Publication WO 2019/236566, incorporated herein by reference) was identified and RGN was converted into a nickase variant (nAPG07433.1; SEQ ID NO: 42). Nickase variants of RGN are referred to herein as "nRGN". It should be understood that any nickase variant of RGN can be used to produce the fusion proteins of the present invention.

For mammalian expression, the codon-optimized deaminase and nRGN nucleotide sequences were synthesized as fusion proteins with an N-terminal nuclear localization tag and cloned into a pTwist CMV (Twist Biosciences) expression plasmid. Each fusion protein has, starting at the amino terminus, a SV40 NLS (SEQ ID NO: 43), a 3X FLAG tag (SEQ ID NO: 44) operably linked to its C-terminal end, operable at its C-terminal end a deaminase operably linked to its C-terminal end, a peptide linker operably linked to its C-terminal end (SEQ ID NO: 442), nRGN operably linked to its C-terminal end (eg, nAPG07433 with SEQ ID NO: 42. 1), and finally a nucleoplasmin NLS (SEQ ID NO: 46) operably linked to its C-terminal end. The codon-optimized nAPG07433.1 and peptide linker nucleotide sequences for mammalian expression are presented as SEQ ID NOs: 486 and 487, respectively. Table 10 shows the fusion proteins produced and tested for activity. All fusion proteins contain at least one NLS and 3X FLAG tag as described above.

Table 10: Fusion protein sequences with N-terminal SV40 NLS, 3X FLAG tag and C-terminal nucleoplasmin NLS

An expression plasmid containing an expression cassette encoding the sgRNA was also produced. Table 11 shows human genome target sequences and sgRNA sequences for guiding fusion proteins to genome targets.

Table 11: Guide RNA sequences

500 ng of a plasmid containing an expression cassette containing the coding sequence for the fusion protein shown in Table 10 and 500 ng of a plasmid containing an expression cassette encoding the sgRNA shown in Table 11 were prepared using Lipofectamine 2000 Reagent (Life Technologies) was used to co-transfect into HEK293FT cells at 75-90% confluency in 24-well plates. Cells were then incubated at 37° C. for 72 hours. After incubation, genomic DNA was then extracted using Nucleospin 96 tissue (Macherey-Nagel) according to the manufacturer's protocol. Genomic regions flanking the targeted genomic sites were PCR amplified using the primers in Table 11, and the products were purified using the ZR-96 DNA Clean and Concentrator (Zimo Research) according to the manufacturer's protocol. Purified PCR products were subjected to next-generation sequencing on an Illumina MiSeq. Typically, 100,000 250 bp paired-end reads (2 x 100,000 reads) are generated per amplicon. Reads were analyzed using CRISPResso (Pinello, et al. 2016 Nature Biotech, 34:695-697) to calculate edit rates. Output alignments were analyzed for INDEL formation or introduction of specific adenine mutations.

Table 12 shows all adenine base edits for each adenine deaminase fusion in Table 10 and guide RNA from Table 11. Tables 13-27 show specific nucleotide mutation profiles for selected exemplary samples. Editing rates for adenine in or close to the target sequence are indicated. “A5” represents, for example, an adenine at position 5 of the target sequence. The position of each nucleotide in the target sequence was determined by numbering the first nucleotide in the target sequence closest to the PAM as position 1 (which is 3' of the target for APG07433.1), the position number being 5' from the PAM sequence. It increases. The table also indicates which nucleotides the adenine was changed to, and at what rate. For example, Table 13 shows that for the LPG50148-nAPG07433.1 fusion protein, the adenine at position 13 was mutated to guanine at a rate of 9.7%.

Table 12: Estimates of base editing rates for each adenine deaminase

Table 13: A>N edit rate using deaminase LPG50148 and guide SGN000139

LPG50140, LPG50146 and LPG50148 showed detectable A>G transitions at positions A12 and A13. LPG50148 showed >9% editing at position A13.

Table 14: A>N edit rate using deaminase LPG50148 and guide SGN000143

LPG50140, LPG50146 and LPG50148 showed detectable A>G transitions at positions A9, A11 and A14. LPG50148 showed more than 11% editing at position A11.

Table 15: A>N edit rate using deaminase LPG50148 and guide SGN000186

LPG50140, LPG50146 and LPG50148 showed detectable A>G transitions at positions A9, A16 and A18. LPG50148 showed more than 23% editing at positions A9 and A16.

Table 16: A>N edit rate using deaminase LPG50148 and guide SGN000194

LPG50140, LPG50146 and LPG50148 showed detectable A>G transitions at positions A13 and A15. LPG50148 showed more than 12% editing at positions A13 and A15.

Table 17: A>N edit rate using deaminase LPG50148 and guide SGN000930

LPG50140, LPG50146 and LPG50148 showed detectable A>G transitions at positions A10, A14, A15, A16, A20 and A21. LPG50148 showed more than 2% editing at positions A10, A14, A16, A20 and A21.

Table 18: A>N edit rate using deaminase LPG50146 and guide SGN000139

LPG50140, LPG50146 and LPG50148 showed detectable A>G transitions at positions A12 and A13. LPG50146 showed more than 4% editing at position A13.

Table 19: A>N edit rate using deaminase LPG50146 and guide SGN000143

LPG50140, LPG50146 and LPG50148 showed detectable A>G transitions at positions A9, A11 and A14. LPG50146 showed more than 8% editing at position A11.

Table 20: A>N edit rate using deaminase LPG50146 and guide SGN000186

LPG50140, LPG50146 and LPG50148 showed detectable A>G transitions at positions A9, A16 and A18. LPG50146 showed more than 13% editing at position A16.

Table 21: A>N edit rate using deaminase LPG50146 and guide SGN000194

LPG50140, LPG50146 and LPG50148 showed detectable A>G transitions at positions A13 and A15. LPG50146 showed more than 3% editing at positions A13 and A15.

Table 22: A>N edit rate using deaminase LPG50146 and guide SGN000930

LPG50140, LPG50146 and LPG50148 showed detectable A>G transitions at positions A10, A14, A15, A16, A20 and A21. LPG50146 showed more than 2% editing at positions A14 and A16.

Table 23: A>N edit rate using deaminase LPG50140 and guide SGN000139

LPG50140, LPG50146 and LPG50148 showed detectable A>G transitions at positions A12 and A13. LPG50140 showed more than 5% editing at position A13.

Table 24: A>N edit rate using deaminase LPG50140 and guide SGN000143

LPG50140, LPG50146 and LPG50148 showed detectable A>G transitions at positions A9, A11 and A14. LPG50140 showed 14% editing at position A11.

Table 25: A>N edit rate using deaminase LPG50140 and guide SGN000186

LPG50140, LPG50146 and LPG50148 showed detectable A>G transitions at positions A9, A16 and A18. LPG50140 showed more than 9% editing at positions A9 and A16.

Table 26: A>N edit rate using deaminase LPG50140 and guide SGN000194

LPG50140, LPG50146 and LPG50148 showed detectable A>G transitions at positions A13 and A15. LPG50140 showed more than 6% editing at positions A13 and A15.

Table 27: A>N edit rate using deaminase LPG50140 and guide SGN000930

LPG50140, LPG50146 and LPG50148 showed detectable A>G transitions at positions A10, A14, A15, A16, A20 and A21. LPG50140 showed more than 1% editing at positions A14 and A16.

Table 28 below shows the average editing rate for LPG50148-nAPG07433.1 in several guides tested in HEK293T cells by lipofection of the two plasmids. The base editing agent was coded on one plasmid and the guide RNA was coded on a second plasmid. The percentage of total substitution at the target is used to determine the rate of base editing.

Table 28: Average Edit Rate for LPG50148-nAPG07433.1

LPG50148-nAPG07433.1 exhibits editing in many different guides across the genome.

Table 29 shows the edit rate of adenine bases in each guide from LPG50148-nAPG07433.1. Only the adenine positions are shown below. Adenine conversion is the average of multiple experiments where appropriate.

Table 29: Edit rate of A nucleotides in mammalian cells for the top 10 guides

LPG50148-nAPG07433.1 shows adenine base editing at positions 6 to 21 of the target region depending on the guide RNA used. The editing rate depends on the guide RNA used.

Example 4: Class I Cystic Fibrosis Correction of Nonsense Mutations

Example 4.1: Identification of RGN and guide RNA

Cystic fibrosis is usually caused by deleterious mutations in the CFTR gene (SEQ ID NO: 51). Six of the most common nonsense mutations are G542X, W1282X, R553X, R1162X, E60X, R785X, and Q493X. Each of these stop mutations can be edited to restore the coding codon by the RGN-deaminase fusion proteins described herein. To target each mutation, the following must be determined: 1) RGN with the PAM recognition site proximal to the nonsense mutation; and 2) a guide RNA that optimally targets the RGN-deaminase fusion protein to the target DNA. Table 30 below shows the number of nickase variants of RGN with PAMs proximal to each of the six nonsense mutations and the number of guide RNAs that can be used for each RGN. Table 31 lists the loci for each guide RNA. PAM recognition sites for each locus are underlined. The target sequence for the guide RNA and the guide RNA sequence itself are also indicated.

Table 30: Number of guide RNAs for nonsense mutations in RGN nickase and CFTR

Table 31: Guide RNA for nonsense mutations in CFTR

Table 28 of Example 3 provides editing data for the SGN001101 sgRNA targeting CFTR.

To assay for the activity of other guide RNAs, guide RNAs in Table 31 were provided with the corresponding nickase variants of each of the RGNs listed in Table 30 operably linked to the deaminase of the present invention to produce fusion proteins. It is recognized that nuclease inactive variants of each RGN can also be similarly tested. Each guide and fusion protein combination was assayed for editing ability at the target site in 16HBE14o-immortalized bronchial epithelial cells. Currently, three HBE cell lines containing CFTR nonsense mutations are available (Cystic Fibrosis Foundation, Lexington, MA). These cell lines were used to assay the G542X, W1282X and R1162X nonsense mutation targets and compared to the 16HBE14o- cell line. Fusion proteins and guide RNAs are delivered to cells as ribonucleoproteins (RNPs), which are described in Valley et al. (Valley et al., 2019. J Cyst Fibros 18, 476-483, incorporated herein by reference). were nucleofected into the 16HBE14o- cell line according to the culture and transformation methods provided in . The guide RNA is provided as a single guide RNA or as a 1:1 or 1:1.2 molar ratio of a tracrRNA:crRNA duplex with RGN protein. Nucleofection of RNP into cells is performed on a Lonza 4D-nucleofector. Cells were then incubated at 37° C. for 72 hours. In some embodiments, the fusion protein and gRNA are delivered to cells as RNA molecules, and the fusion protein is encoded in mRNA.

As there are no cell lines available for E60X, R553X, and Q493X, these mutations were assayed in HEK293 cells using a modification of the GFP restoration assay described in Example 2, in which mutant loci containing nonsense mutations were placed in the GFP reading frame. Cloned into 2.

After incubation, genomic DNA was then extracted using NucleoSpin 96 tissue (Machere-Nagel) according to the manufacturer's protocol. Genomic regions flanking the targeted genomic regions were PCR amplified and the products were purified using the ZR-96 DNA Clean and Concentrator (Zimo Research) according to the manufacturer's protocol. The purified PCR product was then sent onto an Illumina MiSeq for next-generation sequencing. Typically, 100,000 250 bp paired-end reads (2 x 100,000 reads) are generated per amplicon. Reads were analyzed using CRISPResso (Pinello, et al. 2016) to calculate edit rates. Output alignments were hand-cured to confirm introduction of the base-edited mutation of interest, and also screened for undesirable INDEL formation.

In addition to the efficiency of base editing, the protein product of the base-edited CFTR gene is evaluated for function. For two of the nonsense mutations, Glu60X and Gly542X, the base edited change from adenine to guanine does not restore the wild-type sequence, since these mutations are caused by conversion of guanine to thymine. The targeted activity of the fusion protein changes Glu60X to Glu60Gln and Gly452X to Gly542Arg. These mutations allow full-length protein to be produced, but the stability and functionality of the CFTR protein are also confirmed.

Example 4.2: RGN manipulation for reduced size

Ideally, both the coding sequence of the RGN-deaminase fusion protein of the invention and the corresponding guide RNA for targeting the fusion protein to the CFTR gene are packaged into a single AAV vector. The generally accepted size limit for AAV vectors is 4.7 kb, but larger sizes can be considered with reduced packing efficiency. The RGN nickases of Table 30 have a coding sequence length of about 3.15-3.45 kB. To ensure that expression cassettes for both the fusion protein and its corresponding guide RNA can fit into AAV vectors, it is preferred to shorten the length of the RGN amino acids and their corresponding nucleic acid coding sequences.

Through alignment with closely related homologs, a unique 8 amino acid region at positions 590-597 was identified in APG07433.1 and its close homolog APG08290.1 (described in WO 2019/236566, SEQ ID NO: : 60). This region, shown as SEQ ID NO: 365 for APG07433.1 and SEQ ID NO: 367 for APG08290.1, was removed from both proteins, resulting in variants RGN APG07433.1-del (SEQ ID NO: 366) and APG08290.1 -del (SEQ ID NO: 368) was generated. These deletion variants and their corresponding wild-type RGNs were assayed for editing activity in HEK293T cells using the guide RNAs indicated in Tables 32 and 33 following a method similar to that described in Example 1. The editing rates of the target sequences are shown in Tables 32 and 33 below.

Table 32: Edit rate for APG07433.1 protein deletion variants

For the targets SGN000169, SGN000173, SGN000186, SGN000927, SGN000930, and SGN001101, the editing rates of the wild-type APG07433.1 protein and the engineered variant were similar. For targets SGN000139, SGN000143, and SGN000194, the editing rate is reduced when engineered variants are used compared to the wild-type protein. For SGN000929 and SGN000935, the editing rate was increased using the engineered APG07433.1 variant compared to the wild-type sequence.

Table 33: Edit rate for APG08290.1 protein deletion variants

N.D. = not determined

The APG08290.1 deletion variant showed editing in all samples where the wild-type APG08290.1 protein also showed editing. The lowest editing rate detected was 0.13% with the engineered protein. Target SGN000926 had the highest edit rate: 9.17%.

A fusion protein comprising APG07433.1-del or APG08290.1-del and the deaminase of the present invention is produced and assayed for base editing activity using a method similar to Example 1.

The fusion protein comprises an RGN and a deaminase linked by a flexible peptide linker such as that set forth as SEQ ID NO:45. The linker of SEQ ID NO: 45 is 16 amino acids long; Reducing this size can reduce the size of the coding sequence of the fusion protein. A peptide linker of less than 16 amino acids is produced, operably linked RGN APG07433.1-del or APG08290.1-del and a deaminase of the present invention, and using a method similar to Example 1 to activate base editing. can be tested for. Since the peptide linker between RGN and deaminase can determine the editing window of the fusion protein, testing of alternative linkers with different lengths and stiffnesses can also lead to improvements in editing efficiency while reducing off-target mutations. . Therefore, the fusion protein with the highest editing rate was then assayed according to a method similar to Example 4.1 to determine the editing efficiency for each CFTR target sequence. The fusion protein-gRNA combination with the highest editing efficiency is selected as the preferred guide for editing at that site and used for AAV vector design.

Example 4.3: AAV Delivery

The coding sequence for the validated fusion protein/gRNA combination with the highest editing rate is packaged into an AAV vector. AAV delivery has multiple benefits, including lack of pathogenicity, low immunogenicity, high transduction rates, and a defined route for construction. In addition, pulmonary AAV administration has been shown to be safe and at least somewhat effective in both single and repeated administrations (Guggino et al., 2017, Expert Opin Biol Ther 17, 1265-1273). After cloning the fusion protein/gRNA combination into an AAV vector, it can be packaged into several different serotypes to optimize tissue specific infectivity. For the treatment of CF, the target for base editing is the striatal apical epithelial cells of the lung, which will enable sustained correction throughout cell turnover. To target the respiratory epithelium, capsids against serotypes AAV1, AAV5 or AAV6 are used since these serotypes have been shown to be highly infective in respiratory epithelial cells (Zabner et al., 2000, J Virol 74, 3852-3858]).

Once AAV vectors are produced, they are transduced into human airway epithelial cells in culture. Three HBE cell lines containing the CFTR G542X, R1162X and W1282X nonsense mutation targets are used to validate constructs for correction of these mutations. Constructs correcting other nonsense mutations are tested using the 16HBE14o- cell line. Different multiplicities of infection (MOIs) are tested. In either case, reversion of the nonsense mutation to the wild-type CFTR sequence is evaluated. After 2-3 days of culture, genomic DNA is harvested, amplicons around the targeted site are generated by PCR, and NGS is performed similarly to the method described in Example 1 to determine the rate of editing at each locus . Because airway epithelial cells are used, rates of AAV transduction and editing are as similar to in vivo processing as possible while using cultured cell systems. AAV with different serotypes are compared to determine which serotype is optimal for delivery of the fusion protein/gRNA into airway cells. The editing rates achieved by AAV introduction of these systems are compared to the RNP editing rates observed in Example 4.2.

Since cell lines for the nonsense mutations R553X, E60X, and Q493X are not available, fusion protein/gRNA systems targeting these mutations were evaluated in wild-type 16HBE14o- cells to allow for AAV introduction at the site of interest, base editor expression, and off- Test against target edit rate. To determine the rate of stop codon correction, mutant loci are cloned into GFP for the GFP restoration assay as described in Example 4.1.

In parallel with determining the rate of editing by NGS, total protein lysates from cells carrying CFTR mutations edited with the fusion protein/gRNA system are collected, and levels of full-length CFTR protein are assessed by Western blotting. To test whether a functional CFTR protein is formed, Devor et al. (2000, Am J Physiol Cell Physiol 279, C461-479, incorporated herein by reference)] and/or [Dousmais et al. (2002, J Gen Physiol 119, 545-559, incorporated herein by reference). In these experiments, edited CFTR mutant cells are treated with forskolin, an activator of adenylate cyclase, to increase intracellular levels of cAMP. Elevated cAMP levels then activate CFTR, and uptake of Cl ⁻ is measured by genetically encoded yellow fluorescent protein based Cl ⁻ sensors or small molecule fluorescent indicators of chloride, such as MQAE. G542X, R1162X, and W1282X edited cell lines are tested in this assay.

To determine the proportion of off-target mutations, a bioinformatic approach tailored with information about the seed region and flexible off-target PAM recognition space of each specific nuclease is used. These pieces of information have been determined bioinformatically for each protein and are used to rank the likelihood of off-target activity for each protein.

To complement off-target bioinformatic predictions, off-target biochemistry via a modified SITE-seq protocol (Cameron et al., 2017, Nat Methods 14, 600-606, incorporated herein by reference) Enemy detection is also performed. Briefly, genomic DNA from human airway epithelial cells is obtained. The DNA is then treated with several different concentrations of the RGN of interest. Any DNA double strand breaks are labeled, optionally isolated, and PCR amplified with adapter sequences allowing for NGS. The sequencing reads are then mapped to the genome, and the "pile-up" of the reads is identified at the site of the double-strand break, indicating the putative off-target location. In a subsequent set of experiments, cells are edited with the RGN or RGN-deaminase fusion protein of interest, and these putative sites are individually sequenced to confirm that they are truly off-targets. Biochemical methods typically overestimate the number of off-targets because chromatin context, DNA accessibility and other factors can affect the efficiency of genome editing agents in living cells. Thus, both bioinformatic and biochemical methods together provide complementary methods for identifying putative off-target sites, but these sites must be validated by amplicon sequencing to obtain an accurate assessment of off-target editing.

Once putative off-target sites have been identified, amplicon sequencing on 16HBE airway epithelial cells edited with the same optimized fusion protein and guide(s) confirms that the off-target profile established for these systems is comparable to the expected profile in patient lungs. are guaranteed to match as closely as possible.

To determine whether the fusion proteins described herein induce changes in cellular RNA, careful analysis of the cellular transcriptome after editing is required. Fortunately, RNA-seq techniques for assessing adenine base-editing off-target effects are commercially available (Grunewald et al., 2017, Nature 569, 433-437; Zhou et al., Nature 571, 275-278 ], both incorporated herein by reference). Briefly, after editing cells with the fusion protein/gRNA system determined in Example 4.2, total cellular mRNA is collected and subjected to RNA-seq. Transcriptomes from edited cells are compared to cells transfected with ABE alone, and significant differences in RNA sequences are identified.

Example 5: Targeted base-editing for correction of causative disease mutations

A database of clinical variants was obtained from the NCBI Clean Bar database available via the World Wide Web at the NCBI Clean Bar website. Pathogenic single nucleotide polymorphisms (SNPs) were identified from this list. Using genomic loci information, CRISPR targets within the regions overlapping and surrounding each SNP were identified. Listed in Table 34 are a selection of SNPs that can be corrected using base editing in combination with RGNs, such as, for example, RGNs or variants thereof listed in Table 30, to target the causative mutation ("Casl Mut."). In Table 34 below, only one alias for each disease is listed. "RS#" corresponds to the RS accession number through the SNP database on the NCBI website. "Allele ID" corresponds to the causal allele accession number. The "Name" column contains the locus identifier, gene name, location of the mutation in the gene, and the change resulting from the mutation.

Table 34: Disease targets for base editing

Example 6: Demonstration of gene editing activity in plant cells

The base-editing activity of the RGN-deaminase fusion proteins of the present invention is demonstrated in plant cells using a protocol adapted from Li, et al., 2013 (Nat. Biotech. 31:688-691). Briefly, an expression cassette capable of expression in plant cells encoding an RGN-deaminase fusion protein operably linked to the SV40 nuclear localization signal (SEQ ID NO: 43), and a plant PDS flanked by appropriate PAM sequences. An expression vector containing a second expression cassette encoding a guide RNA targeting one or more sites within the gene was introduced into Nicotiana benthamiana mesophyll protoplasts using PEG-mediated transformation. Transformed protoplasts were incubated in the dark for up to 36 hours. Genomic DNA was isolated from protoplasts using the DNeasy Plant Mini Kit (Qiagen). The genomic regions flanking the RGN target sites were PCR amplified, the products purified, and the purified PCR products analyzed using next-generation sequencing on an Illumina MiSeq. Typically, 100,000 250 bp paired-end reads (2 x 100,000 reads) are generated per amplicon. Reads were analyzed using CRISPResso (Pinello, et al. 2016 Nature Biotech, 34:695-697) to calculate edit rates. Output alignments were analyzed for INDEL formation or introduction of specific adenine mutations.

Example 7: mRNA delivery test

To determine if the base edits could be delivered in different formats, mRNA delivery was tested into primary T-cells. Purified CD3+ T-cells or PBMCs were thawed and activated using CD3/CD28 beads (ThermoFisher) for 3 days and then nucleofected using Lonza 4D-Nucleofector X units and Nucleocuvette strips . The P3 primary cell kit was used for both mRNA and RNP delivery. Cells were transfected using the EO-115 and EH-115 programs for mRNA and RNP delivery, respectively. Nucleospin tissue genome It was harvested using a DNA isolation kit (Macherey Nagel).

Amplicons surrounding the editing site were generated by PCR using the primers identified in Table 35 and subjected to NGS sequencing using the Illumina Nextera platform using 2x250bp paired end sequencing. The estimated base editing rate was determined by calculating the total substitution rate for each sample. The average and number of samples for each guide tested are shown below.

Table 35: Average edit rate for LPG50148-nAPG07433.1 via mRNA delivery

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Ala Ala Gly Ser Leu Ile Asp Val Leu His His Pro Gly Met Asn His 115 120 125 Arg Val Ala Ile Thr Glu Gly Val Leu Arg Glu Glu Cys Ala Ala Met 130 135 140 Leu Cys Arg Phe Phe Arg Gln Pro Arg Arg Val Phe Asn Ala Leu Lys 145 150 155 160 Lys Pro Ala Gly Asp Pro Thr Ala Phe 165 <210> 4 <211> 172 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="APG08196 protein sequence" <400> 4 Met Ser Asn Pro Glu Leu Asn His Glu Tyr Trp Met Arg Tyr Ala Leu 1 5 10 15 Thr Leu Ala Lys Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asp Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Tyr Asp Thr Thr Leu 65 70 75 80 Tyr Ser Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Arg Leu Val Phe Gly Val Arg Asn Ala Lys Thr Gly 100 105 110 Ala Ala Gly Ser Leu Leu Asp Val Leu His His Pro Gly Met Asn His 115 120 125 His Ile Glu Met Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met 130 135 140 Leu Cys Arg Phe Phe Arg Gln Pro Arg Arg Val Phe Asn Ala Leu Lys 145 150 155 160 Lys Ser Pro Pro Asp Ser Pro Asn Leu Gln Ala Arg 165 170 <210> 5 <211> 169 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="APG06333 protein sequence" <400> 5 Met Ser Asn Pro Glu Leu Thr His Asp His Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Gln Arg Ala Arg Asn Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Gly Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Tyr Asp Thr Val Leu 65 70 75 80 Tyr Ser Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Gln Leu Val Phe Gly Val Arg Asn Ala Lys Thr Gly 100 105 110 Ala Ala Gly Ser Leu Ile Asp Val Leu His His Pro Gly Met Asn His 115 120 125 Arg Val Glu Ile Ile Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met 130 135 140 Leu Cys Arg Phe Phe Arg His Pro Arg Arg Val Phe Asn Ala Leu Lys 145 150 155 160 Lys Asn Ala Gly Thr Ser Pro Thr Gln 165 <210> 6 <211> 166 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="APG06489 protein sequence" <400> 6 Met Ser Asp Thr Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Met Leu Ala Lys Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Lys Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Tyr Asp Thr Thr Leu 65 70 75 80 Tyr Ser Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Asn Leu Val Phe Gly Val Arg Asn Ala Lys Thr Gly 100 105 110 Ala Ala Gly Ser Leu Ile Asp Val Leu His His Pro Gly Met Asn His 115 120 125 Arg Val Glu Ile Ala Glu Gly Val Leu Ala Asp Glu Cys Ser Ala Met 130 135 140 Leu Cys Arg Phe Phe Arg His Pro Arg Arg Val Phe Asn Ala Leu Lys 145 150 155 160 Gln Ala Ala Lys His Asp 165 <210> 7 <211> 171 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="APG08449 protein sequence" <400> 7 Met Ser Asp Ile Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Met Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Tyr Asp Thr Thr Leu 65 70 75 80 Tyr Ser Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly His Leu Val Phe Gly Val Arg Asn Ala Lys Thr Gly 100 105 110 Ala Ala Gly Ser Leu Ile Asp Val Leu His His Pro Gly Met Asn His 115 120 125 Arg Ile Glu Phe Thr Glu Gly Val Leu Ala Asp Glu Cys Ser Gly Met 130 135 140 Leu Cys Arg Phe Phe Arg Tyr Pro Arg Arg Val Phe Asn Thr Leu Lys 145 150 155 160 Gln Ala Ala Lys Ala Asn Pro Pro Ala Ala Gln 165 170 <210> 8 <211> 173 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="APG05174 protein sequence" <400> 8 Met Ser Ile Pro Glu Leu Asn His Asp Val Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Gly Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Tyr Asp Thr Thr Leu 65 70 75 80 Tyr Ser Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Gln Leu Val Phe Gly Val Arg Asn Ala Lys Thr Gly 100 105 110 Ala Ala Gly Ser Leu Met Asp Val Leu His His Pro Gly Met Asn His 115 120 125 Arg Val Glu Ile Thr Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met 130 135 140 Leu Cys Arg Phe Phe Arg Gln Pro Arg Arg Val Phe Asn Ala Leu Lys 145 150 155 160 Lys Pro Ala Gly Asp Pro Ser Ala Leu Gln Asn Asn Arg 165 170 <210> 9 <211> 168 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="APG09102 protein sequence" <400> 9 Met Ser Asn Pro Glu Phe Thr His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Arg Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Tyr Asp Thr Thr Leu 65 70 75 80 Tyr Ser Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Thr Leu Val Phe Gly Val Arg Asn Glu Lys Thr Gly 100 105 110 Ala Ala Gly Ser Leu Met Asp Val Leu Gly His Pro Gly Met Asn His 115 120 125 Gln Val Lys Thr Ile Gly Gly Val Leu Ala Pro Glu Cys Ser Gly Leu 130 135 140 Leu Cys Arg Phe Phe Arg Met Pro Arg Arg Val Phe Asn Gln Gln Lys 145 150 155 160 Ala Glu Leu Lys Ser Ser Gly Asp 165 <210> 10 <211> 167 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="APG05723 protein sequence" <400> 10 Met Ser Asp Ala Glu Leu Thr His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Gln Gln Asn Tyr Arg Leu Tyr Asp Thr Thr Leu 65 70 75 80 Tyr Ser Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Arg Leu Ile Phe Gly Val Arg Asn Ala Lys Thr Gly 100 105 110 Ala Ala Gly Ser Leu Ile Asp Val Leu His His Pro Gly Met Asn His 115 120 125 Arg Val Glu Val Val Glu Gly Ile Leu Arg Asp Glu Cys Ala Gly Met 130 135 140 Leu Cys Arg Phe Phe Arg Gln Pro Arg Arg Val Phe Asn Ala Leu Lys 145 150 155 160 Lys Gly Ala Thr Asp Val Leu 165 <210> 11 <211> 507 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="mammalian codon optimized APG09982" <400> 11 atgagcgacc tggaactgaa tcacgagtac tggatgagac acgccctgca gctggccaag 60 cgggccagag atgagggcga ggtgcccgtg ggcgctgtgc tggtcctgaa caaccaggtg 120 atcggcgaag gctggaacag agccattgga ctgcatgacc caacagccca cgccgaaatc 180 atggccctgc ggcagggcgg cctggtgctg caaaattacc ggctgtacga caccaccctg 240 tatagcacat tcgagccctg cgtgatgtgc tctggtgcta tggtgcacag cagaatcgga 300 accctggtgt ttggcgtgcg gaacgagaag accggcgccg ctggcagcct gatggacgtg 360 ctgaggcatc ctggaatgaa ccaccaggtt cagatcatcg acggcgtgct cgcccctgag 420 tgttctggcc tgctgtgccg gttcttcaga atgcctagaa gagtgttcaa ccagcagaaa 480 gccgaatcca ccagcagccc tggcgac 507 <210> 12 <211> 492 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="mammalian codon optimized APG03724" <400> 12 atgagcaacc ccgagctgac ccacgagcac tggatgcggt acgccctgac actggccaag 60 cgggccagag aggaaggaga agtgccagtg ggcgccgtgc tggtcctcaa caaccaggtg 120 atcggcgaag gctggaatag agccatcggc ctgcatgatc ctacagccca cgccgaaatc 180 atggccctga gacagggcgg cctggtgctg cagaattaca gactgtatga caccaccctg 240 tactccacct tcgagccttg tgtgatgtgc gccggagcta tggtgcactc tagaatcggc 300 cagctggttt tcggcgtgcg gaacgctaaa accggcgctg ctggcagcct gatggacgtg 360 ctgcatcacc ccggcatgaa ccacagaatc gagttcaccg agggagtgct gcgcgacgag 420 tgcgccgcca tgctgtgccg gttcttccgg caacctagaa gggtgtttaa cgccctgaag 480 acaggcaacg cc 492 <210> 13 <211> 507 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="mammalian codon optimized APG09949" <400> 13 atgagcatcc ccgagctgaa tcacgatgtt tggatgcggc acgccctgac cctggccaaa 60 agagccagag aggaaggcga ggtgcctgtg ggtgccgtgc tggtgctgaa cggccaggtg 120 atcggagaag gctggaatag agccattgga ctgcatgatc ctacagccca cgctgaaatc 180 atggccctga gacagggcgg cctggtcctc cagaactaca gactgtacga caccaccctg 240 tactctacct tcgagccttg cgtgatgtgc gccggcgcca tggtgcactc cagaatcggc 300 cagctggtgt tcggcgtgcg gaacgccaag acaggcgctg ctggcagcct gatcgacgtg 360 ctgcatcacc ctggcatgaa ccacagggtg gccatcaccg agggagtgct gcgggaagag 420 tgcgccgcca tgctgtgtag attcttcaga caacctagac gggtcttcaa cgccctgaag 480 aagccagctg gcgaccccac agccttt 507 <210> 14 <211> 516 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="mammalian codon optimized APG08196" <400> 14 atgagcaacc ccgagctgaa tcacgagtac tggatgcggt acgccctgac actggccaag 60 cgggctcggg acgagggcga agtgcccgtg ggagccgtgc tggtgctgaa cgaccaggtg 120 atcggagaag gatggaatag agccatcggc ctgcatgacc ccaccgccca cgccgagatc 180 atggccctgc gccagggcgg cctggttctc cagaactaca ggctgtacga cacaaccctg 240 tattccacct tcgagccttg tgtgatgtgc gccggcgcca tggtgcacag cagaatcggc 300 agactggtct ttggcgtgcg gaacgccaag accggcgctg ctggcagcct gctggacgtg 360 ctgcatcacc ctggcatgaa ccaccacatc gagatggaag aaggcgtgct gagagatgag 420 tgcgccgcta tgctgtgccg gttcttcaga caacctagaa gagtgttcaa cgccctgaag 480 aaatctccac ctgatagccc taatctgcag gccaga 516 <210> 15 <211> 507 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note=" mammalian codon optimized APG06333" <400> 15 atgagcaacc ctgagctgac acacgaccac tggatgcggc acgctctgac cctggcccag 60 cgcgctagaa acgagggaga agtgcctgg ggcgccgtgc tggttctgaa cggccaagtg 120 atcggagagg gctggaatcg ggccatcggc ctgcatgacc ctacagccca cgccgagatt 180 atggccctga gacagggcgg cctggtgctg cagaactaca gactgtacga caccgtgctc 240 tacagcacct tcgagccttg cgtgatgtgc gccggcgcta tggtccactc tagaatcggc 300 cagctggtct ttggcgtgcg gaatgccaag acaggcgccg ccggcagcct gatcgacgtg 360 cttcatcacc ccggaatgaa ccacagagtg gaaatcatcg agggcgtgct gcgggatgaa 420 tgtgccgcta tgctgtgccg gttcttcaga cacccaagaa gggtgttcaa cgccctgaaa 480 aagaacgccg gcaccagccc cacccag 507 <210> 16 <211> 498 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="mammalian codon optimized APG06489" <400> 16 atgagcgaca ccgagctgaa ccacgagtac tggatgcggc acgccctgat gctggctaag 60 cgggccagag atgagggcga agtgcccgtg ggcgccgtgc tggtcctgaa gaaccaggtt 120 atcggagaag gctggaatag agccatcggc ctgcatgacc ctacagccca cgccgagatt 180 atggccctga gacaaggcgg cctggtgctg cagaactaca gactgtacga cacaaccctg 240 tattccacct tcgagccttg tgtgatgtgc gccggcgcca tggtgcactc tagaatcggc 300 aatctggtgt tcggcgtgcg gaacgccaag accggcgctg ctggcagcct gatcgacgtg 360 ctccatcacc ctggaatgaa ccacagagtg gaaatcgccg aaggagtgct ggccgacgaa 420 tgcagcgcca tgctgtgccg gttcttcaga cacccaaggc gggtgtttaa cgccctgaaa 480 caggccgcta agcacgac 498 <210> 17 <211> 513 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="mammalian codon optimized APG08449" <400> 17 atgtctgata tcgagctgaa tcacgagtac tggatgcggc acgccctgat gctggccaag 60 cgggccagag aggaaggcga agtgccagtg ggcgccgtgc tggtgctgaa caaccaggtg 120 atcggagaag gctggaatag agccatcggc ctgcatgatc ctaccgccca cgccgagatc 180 atggccctga gacagggcgg actggtgctg cagaactacc ggctgtacga caccaccctg 240 tacagcacat tcgagccttg tgtgatgtgc gccggagcca tggtgcacag cagaatcggc 300 cacctggttt ttggcgtgcg gaacgccaag accggcgctg ctggcagcct gatcgacgtc 360 ctgcatcacc ctggcatgaa ccacagaatt gaattcacag agggcgtgct cgccgacgag 420 tgctccggca tgctgtgccg gttcttcaga tatcctagaa gggtgttcaa caccctgaag 480 caggccgcta aagccaaccc ccccgccgct caa 513 <210> 18 <211> 519 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="mammalian codon optimized APG05174" <400> 18 atgtctatcc ctgagctgaa ccacgatgtg tggatgcggc acgccctgac actggccaag 60 cgggccagag aagagggaga agtgccagtg ggcgccgtgc tggtgctgaa tggccaggtg 120 atcggcgaag gctggaacag agccatcggc ctgcatgacc ctaccgccca cgccgagatt 180 atggccctgc ggcagggcgg actggtcctg caaaattaca gactgtacga caccacactg 240 tacagcacct ttgagccttg tgtgatgtgc gccggcgcta tggtgcacag cagaatcgga 300 cagctggttt tcggagtgcg gaacgccaaa accggcgccg ctggctccct gatggacgtg 360 ctgcatcacc ccggcatgaa ccatagagtg gaaatcaccg agggcgtcct cagagatgag 420 tgcgctgcta tgctgtgccg gttcttcaga cagcctagac gcgtgttcaa cgccctgaag 480 aagcctgccg gcgaccccag cgccctgcag aacaaccgg 519 <210> 19 <211> 504 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="mammalian codon optimized APG09102" <400> 19 atgagcaacc ccgaattcac ccacgagtac tggatgcggc acgccctgac actggctaga 60 agggcccggg acgagggcga ggtgccagtg ggcgccgtgc tggtgctgaa caaccaggtg 120 atcggagaag gctggaatag agccatcggc ctgcatgatc ctacagccca cgccgaaatc 180 atggccctga gacagggcgg cctggtgctg cagaactacc ggctgtacga caccacactg 240 tatagcacct tcgagccttg cgtgatgtgt agcggagcta tggtgcacag cagaatcggc 300 accctggttt tcggcgtgcg gaacgagaag accggcgccg ctggctctct gatggacgtg 360 ctcggccacc ccggcatgaa ccaccaggtc aagaccatcg gcggagtgct ggcccctgaa 420 tgtagcggcc tgctgtgccg gttcttcaga atgcctagaa gagtgtttaa tcaacagaaa 480 gccgagctga agtcttccgg agat 504 <210> 20 <211> 501 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="mammalian codon optimized APG05723" <400> 20 atgagcgacg ccgagctgac acacgagtac tggatgcggc acgccctgac cctggcccag 60 cgcgccagag atgagggaga agtgcctgg ggcgccgtgc tggtgctgaa caaccaggtg 120 atcggcgaag gctggaatag agccatcgga ctgcatgacc ccaccgccca cgctgaaatc 180 atggccctga gacagggcgg cctggtccag cagaactaca gactgtacga caccaccctg 240 tattccacct tcgagccttg tgtgatgtgc gccggagcta tggtgcacag cagaatcggc 300 agactgattt tcggcgtgcg gaacgccaag acaggcgccg ctggatctct gatcgacgtg 360 ctccatcacc ccggcatgaa ccacagagtt gaggtggtgg aaggcatcct gcgggacgag 420 tgcgccggca tgctgtgccg gttcttcaga caacctaggc gggtctttaa cgccctgaag 480 aaaggcgcta cagatgtgct g 501 <210> 21 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000930 target sequence" <400> 21 gaacaactca aatggaaatg aatat 25 <210> 22 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000186 target sequence" <400> 22 ggacagtgcg catctccctg 20 <210> 23 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000194 target sequence" <400> 23 gccgcacagc attcaggtcg 20 <210> 24 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000143 target sequence" <400> 24 catggcagta cattagagca 20 <210> 25 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000139 target sequence" <400> 25 aggttttaat ggcccagcct 20 <210> 26 <211> 135 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000930 sgRNA sequence" <400> 26 gaacaacuca aauggaaaug aauaugucau aguuccauga aagccaaaag uggcuuugau 60 guuucuauga uaaggguuuc ggcccguggc gucggggauc gccugcccau uccgaugggc 120 uucuccccau uuauu 135 <210> 27 <211> 130 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000186 sgRNA sequence" <400> 27 ggacagugcg caucucccug gucauaguuc cauuaaagcc aaaaguggcu uugauguuuc 60 uaugauaagg guuucgaccc guggcgucgg ggaucgccug cccauugaaa ugggcuucuc 120 cccauuuauu 130 <210> 28 <211> 130 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000194 sgRNA sequence" <400> 28 gccgcacagc auucaggucg gucauaguuc cauuaaagcc aaaaguggcu uugauguuuc 60 uaugauaagg guuucgaccc guggcgucgg ggaucgccug cccauugaaa ugggcuucuc 120 cccauuuauu 130 <210> 29 <211> 130 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000143 sgRNA sequence" <400> 29 cauggcagua cauuagagca gucauaguuc cauuaaagcc aaaaguggcu uugauguuuc 60 uaugauaagg guuucgaccc guggcgucgg ggaucgccug cccauugaaa ugggcuucuc 120 cccauuuauu 130 <210> 30 <211> 130 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000139 sgRNA sequence" <400> 30 agguuuuaau ggcccagccu gucauaguuc cauuaaagcc aaaaguggcu uugauguuuc 60 uaugauaagg guuucgaccc guggcgucgg ggaucgccug cccauugaaa ugggcuucuc 120 cccauuuauu 130 <210> 31 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000930 FWD primer" <400> 31 gacagccaag aggttttgcc 20 <210> 32 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000930 REV primer" <400> 32 ctgtcccttg cagcttctgt 20 <210> 33 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000186 FWD primer" <400> 33 tggcccctat gtggagatca 20 <210> 34 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000186 REV primer" <400> 34 ggcagagctc agcctcatag 20 <210> 35 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000194 FWD primer" <400> 35 atgacattca ggccacagtg 20 <210> 36 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000194 REV primer" <400> 36 cttcctccta ttcaggccca 20 <210> 37 <211> 19 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000143 FWD primer" <400> 37 acatttgacg agcagcgaa 19 <210> 38 <211> 22 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000143 REV primer" <400> 38 agggcccctg gagaggtttt aa 22 <210> 39 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000139 FWD primer" <400> 39 cttgtagctg gaggtccatc 20 <210> 40 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000139 REV primer" <400> 40 tgttggcaaa tctagtctcg 20 <210> 41 <211> 1071 <212> PRT <213> Bacillus sp. <220> <221> source <223> /note="Bacillus sp. APG07433.1" <400> 41 Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu Asp Ile Gly Thr Asn Ser 1 5 10 15 Ile Gly Trp Gly Val Ile Glu Leu Ser Trp Asn Lys Asp Arg Glu Arg 20 25 30 Tyr Glu Lys Val Arg Ile Val Asp Gln Gly Val Arg Met Phe Asp Arg 35 40 45 Ala Glu Met Pro Lys Thr Gly Ala Ser Leu Ala Glu Pro Arg Arg Ile 50 55 60 Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys Ser Gln Arg Lys Lys 65 70 75 80 Asn Ile Arg Asn Leu Leu Val Gln His Gly Val Ile Thr Gln Glu Glu 85 90 95 Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys Ser Met Asp Ile Trp Gly 100 105 110 Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn His Phe Glu Trp Ala 115 120 125 Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly Phe Lys Ser Asn Arg 130 135 140 Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly Lys Val Leu Ser Ser Ile 145 150 155 160 Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr Arg Thr Val Gly Glu Met 165 170 175 Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr Asp Arg Lys Arg Asn Ser 180 185 190 Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala Glu Leu Glu Lys Glu 195 200 205 Ile Val Thr Leu Phe Ala Ala Gln Arg Arg Phe Gln Ser Pro Tyr Ala 210 215 220 Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln Ile Trp Thr His Gln Leu 225 230 235 240 Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys Val Gly Tyr Cys Ser 245 250 255 Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys Ala Thr Tyr Thr Phe 260 265 270 Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg Thr Arg Leu Gly Pro 275 280 285 Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg Glu Ile Ile Leu Asn Asn 290 295 300 Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys Thr Ile Pro Glu Val 305 310 315 320 Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu Asp Glu Thr Ile Gln 325 330 335 Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu Leu Lys Lys Ile Glu 340 345 350 Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr Glu Ile Asn Lys Val 355 360 365 Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu Thr Phe Ser Thr Leu Asp 370 375 380 Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val Tyr Lys Thr Asp Lys Asp 385 390 395 400 Ile Arg Ser Tyr Leu Lys Ser Ser His Asn Leu Pro Lys Arg Cys Tyr 405 410 415 Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser Leu Ser Tyr Thr Lys Phe 420 425 430 Gly His Leu Ser Leu Lys Ala Ile Asn His Val Leu Ser Ile Met Gln 435 440 445 Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp Gln Leu Gly Tyr Asp Thr 450 455 460 Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys Phe Leu Pro Pro Ile Ser 465 470 475 480 Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala Leu Thr Gln Ala Arg 485 490 495 Lys Val Val Asn Ala Ile Ile Arg Arg His Gly Ser Pro His Ser Val 500 505 510 His Ile Glu Leu Ala Arg Glu Leu Ser Lys Asn His Asp Glu Arg Thr 515 520 525 Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr Lys Lys Asn Lys Gly Ala 530 535 540 Ile Ser Ile Leu Ser Glu His Gly Ile Leu Asn Pro Thr Gly Tyr Asp 545 550 555 560 Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly Glu Arg Cys Ala Tyr 565 570 575 Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe Phe Asn Glu Leu Lys Lys 580 585 590 Glu Arg Asn Gly Ala Pro Ile Leu Glu Val Asp His Ile Leu Pro Tyr 595 600 605 Ser Gln Ser Phe Ile Asp Ser Tyr His Asn Lys Val Leu Val Tyr Ser 610 615 620 Asp Glu Asn Arg Lys Lys Gly Asn Arg Ile Pro Tyr Thr Tyr Phe Leu 625 630 635 640 Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu Arg Tyr Val Arg Ser Asn 645 650 655 Lys Phe Phe Ser Lys Lys Lys Arg Glu Tyr Leu Leu Lys Arg Ala Tyr 660 665 670 Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu Arg His Leu Asn Asp Thr 675 680 685 Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe Ile Glu Gln Asn Leu Gln 690 695 700 Phe Lys Glu Ala Glu Asp Asn Pro Arg Lys Arg Arg Val Gln Thr Val 705 710 715 720 Asn Gly Val Ile Thr Ala His Phe Arg Lys Arg Trp Gly Leu Glu Lys 725 730 735 Asp Arg Gln Glu Thr Tyr Leu His His Ala Met Asp Ala Ile Ile Val 740 745 750 Ala Cys Thr Asp His His Met Val Thr Arg Val Thr Glu Tyr Tyr Gln 755 760 765 Ile Lys Glu Ser Asn Lys Ser Val Lys Lys Pro Tyr Phe Pro Met Pro 770 775 780 Trp Glu Gly Phe Arg Asp Glu Leu Leu Ser His Leu Ala Ser Gln Pro 785 790 795 800 Ile Ala Lys Lys Ile Ser Glu Glu Leu Lys Ala Gly Tyr Gln Ser Leu 805 810 815 Asp Tyr Ile Phe Val Ser Arg Met Pro Lys Arg Ser Ile Thr Gly Ala 820 825 830 Ala His Lys Gln Thr Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly 835 840 845 Lys Thr Ile Ile Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp 850 855 860 Glu Asn Gly Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr 865 870 875 880 Tyr Glu Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys 885 890 895 Lys Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly 900 905 910 Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe Val 915 920 925 Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val Arg Val 930 935 940 Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile Tyr Val 945 950 955 960 Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val Val Ala Ser Ser 965 970 975 Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser Phe Thr Phe Lys 980 985 990 Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu Val Lys Gly Asp Glu 995 1000 1005 Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp Ile Asp Ser Asp Arg 1010 1015 1020 Leu Asn Phe Lys Asp Val Asn Lys Pro Ser Lys Lys Asn Glu Tyr 1025 1030 1035 Arg Tyr Ser Leu Lys Thr Ile Glu Asp Leu Glu Lys Tyr Glu Val 1040 1045 1050 Gly Val Leu Gly Asp Leu Arg Leu Val Arg Lys Glu Thr Arg Arg 1055 1060 1065 Asn Phe His 1070 <210> 42 <211> 1071 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="nAPG07433.1" <400> 42 Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu Ala Ile Gly Thr Asn Ser 1 5 10 15 Ile Gly Trp Gly Val Ile Glu Leu Ser Trp Asn Lys Asp Arg Glu Arg 20 25 30 Tyr Glu Lys Val Arg Ile Val Asp Gln Gly Val Arg Met Phe Asp Arg 35 40 45 Ala Glu Met Pro Lys Thr Gly Ala Ser Leu Ala Glu Pro Arg Arg Ile 50 55 60 Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys Ser Gln Arg Lys Lys 65 70 75 80 Asn Ile Arg Asn Leu Leu Val Gln His Gly Val Ile Thr Gln Glu Glu 85 90 95 Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys Ser Met Asp Ile Trp Gly 100 105 110 Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn His Phe Glu Trp Ala 115 120 125 Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly Phe Lys Ser Asn Arg 130 135 140 Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly Lys Val Leu Ser Ser Ile 145 150 155 160 Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr Arg Thr Val Gly Glu Met 165 170 175 Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr Asp Arg Lys Arg Asn Ser 180 185 190 Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala Glu Leu Glu Lys Glu 195 200 205 Ile Val Thr Leu Phe Ala Ala Gln Arg Arg Phe Gln Ser Pro Tyr Ala 210 215 220 Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln Ile Trp Thr His Gln Leu 225 230 235 240 Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys Val Gly Tyr Cys Ser 245 250 255 Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys Ala Thr Tyr Thr Phe 260 265 270 Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg Thr Arg Leu Gly Pro 275 280 285 Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg Glu Ile Ile Leu Asn Asn 290 295 300 Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys Thr Ile Pro Glu Val 305 310 315 320 Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu Asp Glu Thr Ile Gln 325 330 335 Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu Leu Lys Lys Ile Glu 340 345 350 Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr Glu Ile Asn Lys Val 355 360 365 Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu Thr Phe Ser Thr Leu Asp 370 375 380 Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val Tyr Lys Thr Asp Lys Asp 385 390 395 400 Ile Arg Ser Tyr Leu Lys Ser Ser His Asn Leu Pro Lys Arg Cys Tyr 405 410 415 Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser Leu Ser Tyr Thr Lys Phe 420 425 430 Gly His Leu Ser Leu Lys Ala Ile Asn His Val Leu Ser Ile Met Gln 435 440 445 Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp Gln Leu Gly Tyr Asp Thr 450 455 460 Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys Phe Leu Pro Pro Ile Ser 465 470 475 480 Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala Leu Thr Gln Ala Arg 485 490 495 Lys Val Val Asn Ala Ile Ile Arg Arg His Gly Ser Pro His Ser Val 500 505 510 His Ile Glu Leu Ala Arg Glu Leu Ser Lys Asn His Asp Glu Arg Thr 515 520 525 Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr Lys Lys Asn Lys Gly Ala 530 535 540 Ile Ser Ile Leu Ser Glu His Gly Ile Leu Asn Pro Thr Gly Tyr Asp 545 550 555 560 Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly Glu Arg Cys Ala Tyr 565 570 575 Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe Phe Asn Glu Leu Lys Lys 580 585 590 Glu Arg Asn Gly Ala Pro Ile Leu Glu Val Asp His Ile Leu Pro Tyr 595 600 605 Ser Gln Ser Phe Ile Asp Ser Tyr His Asn Lys Val Leu Val Tyr Ser 610 615 620 Asp Glu Asn Arg Lys Lys Gly Asn Arg Ile Pro Tyr Thr Tyr Phe Leu 625 630 635 640 Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu Arg Tyr Val Arg Ser Asn 645 650 655 Lys Phe Phe Ser Lys Lys Lys Arg Glu Tyr Leu Leu Lys Arg Ala Tyr 660 665 670 Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu Arg His Leu Asn Asp Thr 675 680 685 Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe Ile Glu Gln Asn Leu Gln 690 695 700 Phe Lys Glu Ala Glu Asp Asn Pro Arg Lys Arg Arg Val Gln Thr Val 705 710 715 720 Asn Gly Val Ile Thr Ala His Phe Arg Lys Arg Trp Gly Leu Glu Lys 725 730 735 Asp Arg Gln Glu Thr Tyr Leu His His Ala Met Asp Ala Ile Ile Val 740 745 750 Ala Cys Thr Asp His His Met Val Thr Arg Val Thr Glu Tyr Tyr Gln 755 760 765 Ile Lys Glu Ser Asn Lys Ser Val Lys Lys Pro Tyr Phe Pro Met Pro 770 775 780 Trp Glu Gly Phe Arg Asp Glu Leu Leu Ser His Leu Ala Ser Gln Pro 785 790 795 800 Ile Ala Lys Lys Ile Ser Glu Glu Leu Lys Ala Gly Tyr Gln Ser Leu 805 810 815 Asp Tyr Ile Phe Val Ser Arg Met Pro Lys Arg Ser Ile Thr Gly Ala 820 825 830 Ala His Lys Gln Thr Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly 835 840 845 Lys Thr Ile Ile Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp 850 855 860 Glu Asn Gly Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr 865 870 875 880 Tyr Glu Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys 885 890 895 Lys Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly 900 905 910 Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe Val 915 920 925 Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val Arg Val 930 935 940 Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile Tyr Val 945 950 955 960 Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val Val Ala Ser Ser 965 970 975 Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser Phe Thr Phe Lys 980 985 990 Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu Val Lys Gly Asp Glu 995 1000 1005 Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp Ile Asp Ser Asp Arg 1010 1015 1020 Leu Asn Phe Lys Asp Val Asn Lys Pro Ser Lys Lys Asn Glu Tyr 1025 1030 1035 Arg Tyr Ser Leu Lys Thr Ile Glu Asp Leu Glu Lys Tyr Glu Val 1040 1045 1050 Gly Val Leu Gly Asp Leu Arg Leu Val Arg Lys Glu Thr Arg Arg 1055 1060 1065 Asn Phe His 1070 <210> 43 <211> 7 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic peptide" <220> <221> source <223> /note="SV40 NLS" <400> 43 Pro Lys Lys Lys Arg Lys Val 1 5 <210> 44 <211> 22 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic peptide" <220> <221> source <223> /note="3X Flag tag" <400> 44 Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr 1 5 10 15 Lys Asp Asp Asp Asp Lys 20 <210> 45 <211> 16 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic peptide" <220> <221> source <223> /note="peptide linker" <400> 45 Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser 1 5 10 15 <210> 46 <211> 16 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic peptide" <220> <221> source <223> /note="Nucleoplasmin NLS" <400> 46 Lys Arg Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1 5 10 15 <210> 47 <211> 723 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="GFP-stop coding sequence" <400> 47 atggtgtcta agggcgagga actgttcacc ggcgtggtgc ccatcctggt ggaactggac 60 ggggatgtga acggccacaa gttcagcgtg tccggcgagg gagagggcga cgccacatac 120 ggcaagctga ccctgaaatt catctgcacc acaggaaagc tccccgtgcc ttgacctacc 180 ctggtcacca ccctgacgta cggcgtgcaa tgtttcagcc gctaccccga ccacatgaaa 240 cagcacgact ttttcaaaag cgccatgcct gagggctacg tgcaagagcg gaccatcttc 300 ttcaaggacg acggaaatta caagaccaga gccgaggtga agttcgaggg cgacaccctg 360 gtgaatagaa tcgagctgaa gggcatcgac ttcaaggaag atggcaacat cctgggccac 420 aagctggaat acaactacaa cagccacaac gtgtacatca tggccgacaa gcagaagaac 480 ggcatcaagg tgaacttcaa gatcagacac aacatcgagg acggcagcgt gcaactggcc 540 gatcattacc agcagaacac ccctatcggc gatggtcctg tgctgctgcc tgacaaccac 600 tacctgagca cccagagcgc cctgtctaaa gatcctaacg agaagcggga ccacatggtc 660 ctgctggaat tcgtgaccgc cgctggcata acactcggca tggacgagct gtacaagtaa 720 tga 723 <210> 48 <211> 141 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="GFP-stop guide RNA" <400> 48 ggcuccccgu gccuugaccu acccugguca uaguuccaug aaagccaaaa guggcuuuga 60 uguuucuaug auaaggguuu cggcccgugg cgucggggau cgccugccca uuccgauggg 120 cuucucccca uuuauuuuuu u 141 <210> 49 <211> 9 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic peptide" <220> <221> source <223> /note="meganuclease motif" <400> 49 Leu Ala Gly Leu Ile Asp Ala Asp Gly 1 5 <210> 50 <211> 318 <212> DNA <213> Homo sapiens <220> <221> source <223> /note="Homo sapiens Human RNA pol III U6 promoter" <400> 50 tgtacaaaaa agcaggcttt aaaggaacca attcagtcga ctggatccgg taccaaggtc 60 gggcaggaag agggcctatt tcccatgatt ccttcatatt tgcatatacg atacaaggct 120 gttagagaga taattagaat taatttgact gtaaacacaa agatattagt acaaaatacg 180 tgacgtagaa agtaataatt tcttgggtag tttgcagttt taaaattatg ttttaaaatg 240 gactatcata tgcttaccgt aacttgaaag tatttcgatt tcttggcttt atatatcttg 300 tggaaaggac gaaacacc 318 <210> 51 <211> 32701 <212> DNA <213> Homo sapiens <220> <221> source <223> /note="Homo sapiens CFTR gene" <400> 51 aattggaagc aaatgacatc acagcaggtc agagaaaaag ggttgagcgg caggcaccca 60 gagtagtagg tctttggcat taggagcttg agcccagacg gccctagcag ggacccccagc 120 gcccgagaga ccatgcagag gtcgcctctg gaaaaggcca gcgt tgtctc caaacttttt 180 ttcaggtgag aaggtggcca accgagcttc ggaaagacac gtgcccacga aagaggaggg 240 cgtgtgtatg ggttgggttt ggggtaaagg aataagcagt ttttaaaaag atgcgctatc 300 attcattgtt ttgaaagaaa atgtgggtat tgtagaataa aacagaaagc attaagaaga 360 gatggaagaa tgaactgaag ctgattgaat agagagccac atctacttgc aactgaaaag 420 ttagaatctc aagactcaag tacgctacta tgcacttgtt ttatttcatt tttctaagaa 480 actaaaaata cttgttaata agtacctaag tatggtttat tggttttccc ccttcatgcc 540 ttggacactt gattgtcttc ttggcacata caggtgccat gcctgcatat agtaagtgct 600 cagaaaacat ttcttgactg aattcagcca acaaaaattt tggggtaggt agaaaatata 660 tgcttaaagt attattgtt atgagactgg atatatctag tatttgtcac aggtaaatga 720 ttcttcaaaa attgaaagca aatttgttga aatatttatt ttgaaaaaag ttacttcaca 780 agctataaat tttaaaagcc ataggaatag ataccgaagt tatatccaac tgacatttaa 840 taaattgtat tcatagccta atgtgatgag ccacagaagc ttgcaaactt taatgagatt 900 ttttaaaata gcatctaagt tcggaatctt aggcaaagtg ttgttagatg tagcacttca 960 tatttgaagt gttctttgga tattgcatct actttgttcc tgttatata ctggtgtgaa 1020 tgaatgaata ggtactgctc tctcttggga cattacttga cacataatta cccaatgaat 1080 aagcatactg aggtatcaaa aaagtcaaat atgttataaa tagctcatat atgtgtgtag 1140 gggggaagga atttagcttt cacatctctc ttatgtttag t tctctgcat gtgcagttaa 1200 tcctggaact ccggtgctaa ggagagactg ttggcccttg aaggagagct cctccctgtg 1260 gatgagagag aaggacttta ctctttggaa ttatcttttt gtgttgatgt tatccacctt 1320 ttgttactcc acctataaaa tcggcttatc tattgatctg ttttcctagt ccttataaag 1380 tcaaaatgtt aattggcata aattatagac tttttttag c agagaacttt gaggaaccta 1440 aatgccaacc agtctaaaaa tgcagttttc agaagaatga atatttcatg gatagttcta 1500 aatactaatg aactttaaaa tagcttacta ttgatctgtc aaagtgggtt tttatataat 1560 tttcttttta caaatcacct g acacattta atataggtta aaaaatgcta tcaggctggt 1620 ttgcaaagaa aatgtattac aaaggctgct aagtgtgtta agagcatact catttctgtt 1680 a ggcagtatt 1860 gcttagtttt caaagtggta ggctttggag tcagattatt ttgattcaga tcctacatct 1920 actgtttagt agctctgttg cctgaggcag gtcccttaac atctctgtgt gtgacttgac 1980 ctttaaaatt tggagactgt catagggtt aatcccttga gaaaatga at gtgaaaagtt 2040 agcctaatgt taactgctat tattatggat taccatattt tcacattcat cacagtacat 2100 gcaccttgtt aatataagat gctcaattca tctttgagta taattttgg actctcaatc 2160 tggatatgca atgagtgggc ctgtatgaga atttaattta tgaaaaattg tgtttcacat 2220 ggccttacca gatatacagg aaacacgtca catgtttcta ttgtatgttg ttaaatgcct 2280 taga atttaa ctttctgaat aggatccctt cagtttgaga gtcataaaag agtaaaatta 2340 ttatggtatg agttatagat tgtattgaat atctctttat atgtctaggt tttgtcattg 2400 gaaaaccaaa aagtttggaa aaaaaatcta agttatttct tactttctta atttt gtgtg 2460 gatttcacat caagtataaa atttgaagaa catctgaact atcataatcc atatatatat 2520 ataaaataaa cataatctaa gagagaattt caccatgaaa aattcaggta gttcatgact 2580 atcagagcaa acaagtacat taaattgaaa cttttatgaa aataacattt atgaaatagg 2640 aagctatttt taaactagaa gtgatatatt agcatataat ttataattca tatacaagtg 2700 ggattgattt ataaatggtc accaacagag attgtgctat ttaatttggg aaaatttttt 2760 aaatttacat tttctcacaa cttttaaggt agttattcag tttgttcctc tctgtctctt 2820 ctctcatgcc ctgaattttt catatttcgt ttagttgtaa gagtgtatat caaaccgtgt 2880 gtcacatgac ataact tgaa ttttcgtcgt gatatctgg ctatgtctag gtctatactg 2940 aggaactgtg ggaaccccac agaatccaag tatacagtgc cactgatttc ttacaaggga 3000 tgtggggtct cctgtaaact ctgcagttag tctcaagtaa gaccaaagag taaaatattg 3060 ttaggatcta aggtggaaat tcagcaaaga atcacatagt ctaagtctcg agtttaacag 3120 taagataatt tgagatactt ttg taattat taaacacaaa gtaatgagag attttaaaac 3180 aaacaaatac acctgaattt atatatcaga ataggtatgg tggttcaaaa tagctatcta 3240 ataaaaacca cactcctatt ctaaacattt gcctttgatc aaaataattt tgggtctctt 3300 attatgaaat tgccttt cta aataatacat aaatttcttc tcataagtat atattagcca 3360 cattatttta ttgtattgt tttatattca tagcttgctt tagattaaaa attatattac 3420 ccagactggt ctcttggact tgcttccaag tgacttttga ctgtatcaca aaatcaaatt 3480 cactctgaaa atataaagat ttttcatcat aatttccttt gttaacagcc aagtgctacc 3540 taattttagg tgttttcatt aaaaaaa aat gcattgcaaa ctttaaagac aattcttttg 3600 tttgtttgtt tttaaaagac agagtctcac tctgttgccc aggctagagt gcagtgacac 3660 aatcataact cactgcaacc tccacctcct gggctcaagt gagccttcca tcttgcctca 3720 cgagtagctg ggtcttcagg tgtacaggtg tgtaccacca tgcctggcta actttttttt 3780 tttttaagtt atatagagac agtatctcac tatgttgccc aggctgctct atgacc attt tgaatgggac 4020 cacacttatt tggttatata aattatgata cactattaaa aattcatcat gatgattttg 4080 tatttacatt ttatttacat gtttgcaatt tgtgaggaaa gctaaaatta tggctaagcc 4140 ataaatattt ttgcagtttg ttgagggtgt ttgta aaagt gttgccaagg aagaccagtt 4200 ggctacccaa acaagggttt agtctaggtc tgatcaatac atacacatta tctcaggttt 4260 gtctatcaga aaaaccttag gttatccaaa tcaaaataaa atagatgcat aaaacaaagg 4320 ccaatatgg ttgaacaatt atattgtgat atacaactgc caagcattcc cgattaccat 4380 gactccattt agtcagtcca tgggcaaatg ccatcaatga ggacagccca gggttt ccat 4440 attctctctt ggctttacat cctataggaa ttggaggggc ccacctctgg gataggagcc 4500 cttctgtctt gaacaatgtt gtctgaacac taacaaatgt tgactttcta caccagtccc 4560 tcaatagtct tttctattta tccttttgct gaccatgttt tgtta ttaca cagttgagat 4620 ttttcagctg ggaatctgg ttaattttgt attaattttg attagcttaa ctctcagagt 4680 tctaaaagta cctcctgtac ctgatatatg acaaaaatta taattacatt tatttatata 4740 taaaatatct ttgtatatgt aaaatatctt tgtatatata attatataat tgtttctttt 4800 aattttgcaa attttaaaaa gttctccttt gttttgaagt ttattcc tat agttttttat 4860 atgctagtta aattattaat cacttgattc aagtaatatt cttatatact tataaggaat 4920 agtgtagttt taatatttaa ttccttgcta aagagagaag tggaatctat tttcttagc 4980 tacttcatca atattttatg tttgatgtga cagtcaaaat at ccctcaga gctaactgtt 5040 acactaggga aatcacggtt ttccagtttt ccatttatgt gttatggggag ggaggtggaac 5100 ttagtgtaat aatattcaat acataaatgt taacacttgt ttaaaggtcc ttgagtgagt 5160 actgctataa aatgcattat tattgctagt gtcatttcac aagagcctat aatttcagtg 5220 tgatagagct acaatataag tatagtattg caaaaccatc aggaagggtg ttaactattt 5280 agcatgcagt ta tgtgttgg ttgtcaaaac gttaaaaaca tctctgactc agcagcaatt 5340 ttggcaattt tgatcctgag gcatctgtgt agggcatctt cctggagaaa aacctctgag 5400 atgcaatgag gtcaaaaggg gaaaacagac tatgataaag atcaagttgt ttggagatct 546 0 tgtagaaaga ttaatttaca aatatgtcaa gtgcattatc atggaggaaa acattgctat 5520 ttctgttggt tctcttcaga gctctagaat caatttacca catagttgtt tcagtgtgaa 5580 attagcatta cagagtggct ttacggcttt actgtagggc attgtgtcag caaagagctt 5640 aggcttcttt tagcaagaag cttgtaaaaa tttaatttac tcttagattg cttgatgtag 5700 agaattacat tcctac agag ctctgaaaaa tcttttttca gagtttttca cagctgtatt 5760 caagttgcaa ggcttgtcaa ctttgctatt tttctgtgca gctctgttaa cttattatta 5820 tcttttgaca taaattatga ttccaaattg taaagctctg gatgtcaggg ccttttctaa 5880 tttgtttagt atgatattca gaccatttca agactcttcc gtggaacaat ttaataaaga 5940 tttttttg atgttaatga gttcatggtg atcaacccta gagacctgtg tctattgtag 6000 atcgatgaca ttcaacagtc ctgcagtgct ggcatcattt tgataaaaag gggtcaaagc 6060 aagtgggact gtgggcagat ttttaatgct tagaacaatt attccatcga agttttcttg 6120 tgtcccttct gccttag cct ttgtaggata gcatgcttgc taatttcttg ctcatggggt 6180 aaggaaatga agatttttgc taggtccgta ggattattag gactactcag gcctgaagct 6240 atgcctggat atagccagaa aactctccca tagcttgctc caaggagctg agatacagca 6300 gtacttcctt tg taggtcat gattctgggt aacctggaag atgacctcat tcatattctg 6360 tattctatgt gagacgttaa gaaggtagag gtggccaaga aggaaattgt tgctgccttt 6420 atggaacaaa ttatctgaaa cccagctttc tcgagggctt cattgaagta ctcaactggg 6480 gcacttaacc cagtctaagg ctggtcaagg aaggcttgct gggggaagtg tctttgtat 6540 tcacacctaa aggagg ttat tcaattagaa ttatccaaag agggtaggga tgggctagga 6600 aaaatttaaa caggtagtgt ggaggactga caggataagt aagcatggca ccttcaaaat 6660 atcctgagaa gttccctatg acgggaacat aaaatatgtg acagagattt gtgggagatg 6720 ggtctggaa a ctctagcagg ggccagatcg taagggggct ttgtaggctt tgtaggcttt 6780 gtttgggctt tatcatactg gaagtgaaaa gccatggctt ttaaacagga gagggacata 6840 atcagttcat atactgttgc agttttgtaa aagaaaagat gagctgaaag agtggccatg 6900 gtggaggtgg gtggggtggg ggggaggggg cggggagaga gagagagaga gagagatttg 6960 aaagacattt aggaggtaaa atcaactggt ttggtaatca attagtagtt gaaggtgaag 7020 gaaagagaag agttaaggat aacatctata tttgttgatt tggataatag aggggacagt 7080 ggtgctgctt attgaatgag aaaatttaat cggagaagaa ggcatggagc aggagtgcag 7140 acctatgtga ctactacttct ctcaaaacca gaaacggaaa t gatgtaat ggctcagggt 7200 taggtaatat ggttatttga aaatgtatta aagtgattta gagcttagtc ttaggtaaga 7260 gatataagat gtctgaggtg acagttttat aaatatgtag agtgcccact tgtttggcct 7320 tattgtggca tagtgtgacc tgagagtgtt aggaagaagc agctgagttc tagggacagt 7380 actggttaaa ttctacttag aaattatact tagaactctc ctatataacc tgctaactga 7440 tgtctgaacc tcctgataac ttcactcctt taggcagtgc ttttcacatc acgggacaca 7500 acatatgaga gatcatagaa attcaatgg gtatgaaaat ctgcttggga cttcagatat 7560 tgtctccagt gattgaataa aaataggagc tcacctacta tgatga ggtt tctgtgtgtg 7620 ttaaaagaag gttttcatta cttttgaaaa ggttatgtat ccttgtttta tgttaaaact 7680 ttgagctttg ttaaatatgc agagttctct ttcttagcat ggactacaga ggtgcaacta 7740 cctcctacct gacttcacat ctactcccaa atgcctagtg aaggcttaat aatttcaaaa 7800 agggactcta gaatttcatt tgataccagt cagacaaatg tgtgaaaatt aagcataata 7860 ggcagaatcc caggggtact gacagctgta ttaagaggtg attcaagggc taaaccttag 7920 agtccagcat tggttatggg tgtgacaaga aaatgaagcc tatgttggct gggattagca 7980 accacagttc tagaggaagc aaggtggaga aactatatag ggggctccct ttgtacgttt 8040 tatttatttt aaacatctct ataaactcta gaaattaaaa caacaatacc aacacaaaag 8100 catcactttt tcgaccaaag accattgcta tacttttttg tgtaaagggc tagatagtaa 8160 atattttcag ctttgtgggc cacataagtc tctgcaatag acaatatgca aacaaataag 8220 catggctgtg tttcaattaa actttattat gaacattaaa atttgaattt catataactt 8280 a aaatggact 8460 tttcagaaga agaaaatggt agcttaacag ttattagatt attgtccaga ataatttttg 8520 acttataagt ctctgttgac catttcattg cctctttttt tggaatatgc atcttttaat 8580 gtgtccttca aggcaaaggc tctatcttat ctatcttgg tcttgcattt tcccagggca 8640 atgtttttca caattttttt aaaaaacaat actgtaatca attttcaaat aaaattttcc 8700 atgggaccgc agtgtataca aatagcagtg acaataaaag ataataactc tcccataaat 8760 acaaagaaac agttaaccta gtgctctaaa gtaaaggcta cagtgatttt gtataacatt 8820 tatatgtaat tttcttgatc ctacatggtt gtgtttttca cagtgttatg tttctgaaat 8880 cgagatgcct tttataattg atgtcaaaag aaacttgtca gccacaaggc ccaggaataa 8940 gttgtaatat gggaacttag caatacataa aggtatatat actcctgtga cctcagctga 9000 attatttgca ttggttgcat cccacaaggt tgactcttaa ataaatttag tttgttgctt 9060 gaaatttctt gggataaatt actttgtgat gtagttttga aaaaaaaaca ggtaatattt 9120 agtctgaagt ttgtct gaca tactaagcaa tgtaattaaa gtagaagtcg cctaagctca 9180 gcactttatt atgccttgaa attatactgc ctgtcctaca ggtgaaggtg ttatgaatgc 9240 agtttgtcac tgtaactcta ttcatagctc tgaaaggctg agagtgactc agaagaatat 930 0 ttttgctctg aatatgaaga acgcttagac taaaacttta attacgatgc tgaagaagaa 9360 agtggtaggt gattgcatga ataagtatgt aatattgtta atttctaaaa actgtgtata 9420 gttaatgtag tgcttctttt tggaaaggct attgttaaat tgatggtaaa ttctataacc 9480 aatatcacct taaagcaagt acgcatgata aagtattata aaaccatgat aatatcatat 9540 gtggcttatt attgttccct gagtgttgta caactctgtt atgctgtgat gaaacctcat 9600 gcaaacaggt atgtcaaaga tatgatgggc tgttaactga gcttggccca catatggtgt 9660 agtgacatgc tcactaatgc agtgcagaga taaccaataa cagatcataa caggtttaaa 9720 tatgtgcaag gagatgtcag cagaagcttt cctacatagt gaatactaaa caagcctgac 9780 agcccaggat catgttcgga tcaatctagt gtgctaaaat taacatatag tcctacattt 9840 gagaatgtgt gattttcttg gttcctgtct ataaaataat attttaaaat acatacattt 9900 caaatcagaa gttggtgaat tcactgaaat atttctagag aacactaggt attggggctc 9960 atagtgtgaa aaccactgac ttaattcttc ccccatcttg gt tgttcctg atcttccctt 10020 gtgtccccat tccagccatt tgtatcctta gaaaatgatc tcatattcta cttcatcttt 10080 atcttcattg tcaactgtca ggtagcaata tatgatggaa gaagcatgta ctttggaatc 10140 agacagacct ggctggaatc ctaact ctgt cacttattaa caatgtgatc ttaggcaatt 10200 tacttaatct ctctgaacct cagctactct cgtcagtaca atgagttatc cttatcttta 10440 caaaatctgc agtatgggtc agctggcagg aaacccagga gagtcaatgt tccagtttga 10500 gtctgaaggc agtctgttgg ggaatttcgt ccttctctgg gaggccagcc tttttgttct 10560 atacaggcct tcaaccgatt ggatgaagtt cacctttat agtgagggca atctgcttta 10620 accaaagttt actgatttaa atgttaatct catccaaaaa cacccaccca gttgacacat 10680 aaaattaacc atcactctct gtaagcactt tctatgcatt aagtgatagc aaataatgcc 10740 agacataggg cgtctttaat aaatggtaag cactgttatc agcaacaaca ggattattat 10800 aattagcacc ttttcatctt tctgtctggg ctctgagaaa gtacctctct tctctaaatt 10860 tatccctcct ttcctatgaa ttagacccag tgctttctct gaattatgaa ggtcacactc 10920 ctacaaatgc cccttcccaa ttgcacatct gtcggctttc tttgccattg acttttatct 10980 ctagctttta aatttacagg catatgtcag ttaacaatgg gaat gcgttc tgggtaatat 11040 gtccttaggc aattttatcg ttgtgagaat actatagagt atacctacac aagcctagat 11100 gtcgtatagc ctactacaca cctaggcaat atgacatagt cttttgcttc taggctacaa 11160 acctgtacgg cttgttacta tactgaatac tgcaggcagt tgtgacacag tggtatttgc 11220 atatcggaac atgtctaaac acagaaaagg tgcactaaaa atactatgta gtgatctcat 11 280 gggaccacca ttgtatatgc agtctgctgt agactgaaat gtcatgcagt gcataactgt 11340 atcttaaata ctcaaagtat cacctttgtt tgtttgtccc cttgtgtgca tcatcctaac 11400 gtggaatttc tctgttgatt agggccagcg tattagtttg ctagggctac cataacaaaa 11460 taccacaaat ttggtggctt aaataacagg aatttattat cttatggttt tgaagactag 11520 aagtacaaga tcaaggtgtt ggcaggtttt tcttctaagg gccatgagga agagtctatt 11580 ccatgccttt cccctacctt ctggtggttt gctagaaatc cttggcattc cttgacttac 11640 agaggcatca ccctgatctc tgttttcatc ttcacatggc attctccctg tgagcctgtc 11700 tctgtgtcca aacttcttta ctattaatat aaggacacca gtcatattgg attagggtct 11760 actttagtga cctcattgga atgtattac ctctgtaaag atcctatctc taaataaggt 11820 cacatcctta ggtaccgggg gttaggactc aaacatacct ttttttgggg aaacacaatt 118 80 caacctataa caattgataa cactctttag gagcagaatg cgatatggaa gtaatttgag 11940 accataaagt atatacatgt aggggagttaa tctatgaaac ctattgaaag ccatatatac 12000 ctcatgtata gtggtccata aatagcatgg agacattgca gaggatgtta agtgatatga 12060 tacaggaaca atccaagaag gtcataagaa aaaggacctt ttgctcttga gaggactgaa 12120 gaatgacttt ccatttatga aatttt gtcc ctgaac aagtataggc accctcacat ttgcattgca 12360 tttactatag aattgaaaaa tgttttgacc tttttttttt ggcttttaat atatttgacc 12420 aagagtaaca gctaagcaat acctatttgc aatcagtgtc atcatgtggg ctccaaacat 12480 atcatgtttg tgtaattaat tgattgaccc attaatttgt tcaatttctg ctctgttcca 12540 ggcactgaac aacatgatgg agataaaaga ta aatattac acctgccttg tcctcaagaa 12600 gttagtcttc tgagggaaag aaattagcaa acaaattgta atctcagtta tgtgccatgt 12660 tccatgctgg gcacagggga tacagtagtt taaaaaaaac acaagatcta taaggtgttt 12720 cttcttgtgg accttacagt ctagggtgct tggaaacatg gggcgttggc agacaagtaa 12780 atacacattt tgtggtaaag gctcaggtag aagaagtaca ggatagaata gagcacacca 12840 tggggaatta atctagactt cagagaggct cacacataca taatttatgt gtgactattt 12900 caatgcattt gaggtttctt ggaaatagag gttaggtttt attttaagga agttaccatt 12960 ttttttttca gtgtgatgtg gttgaaccaa agaatg ccat gcccagtgat ggtaatagga 13020 taatcttttt aaaaattaag agccacctaa taaatcaata gtttcattca gcgggagctc 13080 ctgcagagtt caaaaagaag agaatctggc acagcgtttc ctttaaagtt cattttccta 13140 gagtgtgaat ggaagcaaga gattataaca ttttgaggtc aaaaaaattc tgaaatgcct 13200 ataaaaatta ttttctccaa attatcatca tttgtgcttt taatgacctg attgcaaaga aaatattaag taaaagggat ttaaagcaag 13440 gcttttgagg tagagtctta ttaattcctt ggtaaacctt gagccaattg ttgtctatgt 13500 tctctgcctc tgtcttgctc cttccttctg ggattcactg tgggaatgcg ggattgttaa 13560 tctggggatg ctgtcc aatc ctgcctctct caagctttgc tattgatctc cctcccagtg 13620 ataataaagc ttgaagaaaa tgaaagtagc gttagtattg gtcctcaaac tcaagaacag 13680 gatgaaactt aaatcttgag tcatacaatt gtgtctacat actgctcccc aaaaagagaa 13740 gtaaagaaga tgctaacttt cccttttaat ttgcagtact tagcaatttg ttttcttgag 13800 ggttaagtaa taacagtgga agaaaaaagg gttaaaatgc caccaagaac ccaatt ccat 13860 gtttagtttg aaagtgggaa atcagctgcc actgggaagt ctgaatccaa tgccatgatg 13920 ttctttgaat ccttctgaga aataatcatg tgtagccata acatacctgt ataacagagc 13980 agagaacata aacaaatgaa ggtgaaggga agattaagac agaagaga aa aattccagaa 14040 tcgactgatc atttttatct gtttagatga tttcaggcag aatcctagag accaacttta 14100 tcacaactga attttaaaaa tcaccagctt tgtcattgtg atgcagcatc agtttcagta 14160 ttatccttgg agtattaatt cttaatcatc ttcatcttag aacatttttg aggtcacttc 14220 tagtctctat ttcaccagtg aagaaacaaa aatccccaaa ctatatcagg tggaattaca 14280 cagtattttt tttttaattt tgggggaaagt cgattcaagg cagtaacttg caagctagtg 14340 ttagaaagga tttaataaat agtggttttt ctgtacacat agtgagaggt cattacatca 14400 tttggttgtt gaaagtcata aggatgtcta gcatgcgctt t gcctgtagt ggttcatgcc 14460 aggcagattc ctgactccta taacccagag cttatcagag catttatgtc cccaaagaga 14520 aatgtcacct ccatctttca ataaacactt tagcaaagaa aaatcaagta ctttaattcc 14580 aaatcttgag ttaattccag aataacaatg atggctcgga aaaatatggg tatttctgtc 14640 aaaggacaga gaaacctagt agagagtatt tactttgggt cctagtgatg gtatctgaac 14700 aagctagg a acaaagagc ctcaataagg gattttgagg tctagaaaaa gagaggaaat 14760 accaaataaa tggaataatt ataaaataaa taccagcaaa gttaaatcaa tatatcatgt 14820 gggagatatc cttatatcac tcatgtgatt tctattttgt tcctatatta ggccaaggag 14880 aggtggaact tgttttcctt tttccctctc agctacgaat ggacatactt aaaactgttt 14940 ctctgcttct gttctctaaa atgtgattgt ctaacagtaa ccgtgatgac gttttgacag 15000 ttgcacaagt ttctttcttt aagctttaaa aatgccagcc agtaacccag tggcatttct 15060 actataaaat cttaaggcca atccatttcc ccttttcctt attttcttgg tttcaaatat 15120 att tttatg ccaatggaaa taaaaatcct aaattagaga gcaatggcat cccttgtctt 15180 gtgaataaag agctcctaaa tgtgaactta tacaggatgc agcaatttat agggtagtta 15240 atcattcttc tttctagcca gttgttccag ctacagtttt gtggctcttg ttagtgg ctt 15300 cattcccaga tagaataaaa atcaaaccaa aatcctggaa aggcactctg aggatgcttc 15360 tctaaagtag atgggcatca actataaatc acaatgcttt gtttcctctg ttatgtttca 15420 agatgggtgg gatttttttt gtagcattac ttattattgc ctctcaagtg cttgagtctt 15480 tgaaatccaa gtcatgtgag tgaattagat acagctgtta gaagtggcct ttcaatgcca 15540 atggtacaca ttcc ttggtt tctttacgat actattgctc ttacaacttt tatctgaagt 15600 cataaattca tagttgtccc agaagttaag ttccttgctt ctagaggaca gaaaacaaac 15660 aatttacaca actcatggtg catgtcacca gtccttagat ctcatgaaat atgcatgaaa 15720 tcttaaat ca cttgctgtag ccacccagcc attgacatat ttgaaagact ttagtgtatc 15780 aaagtcacta taatgaaaat tttgatttca ccagttctag gagtgaaaaa tcaaatgttt 15840 agtaaaactt tctaaaatta acactgacag ttgatttctg tatactgttg ttcttaataa 15900 tagctttatt gagatataat tcatattcaa aacaacttac ccatttaaag catacaatcc 15960 aatgattttt tagtatcttc aaagagttgc ctatcac cat aaccaatttt agaacacttt 16020 catcactgta aaaagaaact ccattcctat tagcagtcat tccttattcc aaatccccct 16080 gctcgcccta gacaactaca aatgtacttt ccatctctat agatttgcct gttctggaaa 16140 ttttatgtaa atagaacaaa gtgttctttt gtgactggct tatttcactt agcatttttt 16200 ttcaaagatt catccctgtt gtagcgtgta tcagtgcatc attctttttt atttttttag 16260 agacagggcc ttgctctgtt gcccaggttg gaatgtgcag tggcatgatc atgggtcact 16320 atagctttga agtcataggc gaaagcggtc ctcccacctc agtctcccga gtagctgaga 16380 ctacaggctt gcaccacatg actgtctaat ttataatttt ctttag at tttattta tcctttcccc agttaataga 16620 tatttcgatt gttcctaatt cttgtctatt ataaataatg gtgctatgaa catttgtgta 16680 caagtttttg tgcagacatc cattttcctt tcttttgggc atatacctac gagtgtaatg 16740 gatgggccat atagtaactt tatgtttaat attttgagga tttttcaaac tgttttccaa 16800 agtggctgca tcattttaaa ttccttccac cattgtgt ga gtgtttcaat ttctccacat 16860 atttgcaaca cttactatta tctactctta aaaattacag ccatcctact gggcatgaag 16920 tggtatttca ttgtgagttt tttttttctt tttctttttt tctttttttg ctaatgtttg 16980 tggatt ttct tttcattttc ttgatggtgt cctttgaagc acaaaagtat ttaattttga 17040 taatttccaa tttatttttt gttattgctg tttgtgcttc tggtgttgta tctaagtgta 17100 tgctacttta aaaaattagt tgtaatatgg caaattggat acatgtgtag gctttggtgt 17160 cacaatccta attttaaaat tctgactctg cccttgacaa attaactaat taagcttcct 17220 tagcctcagt ttctcaactg taagttggag atattaccaa gacctacctc ttgaattgtt 17280 gtggggatca gatgaaataa tgtatgtgaa atatttagaa ttatgcaagt ctgtggtaat 17340 gaatactaat gttagctatc attattgtta taatcccaat aataaattct ggtgctttga 17400 aaattaaacc aaagccaagc agttgatatg aagaagcatg taataatgta cagacataat 174 60 gctttataga caacattgaa tttggctctc atgaaca ggaatagtgg tcatggtagt 17520 tattatctcc agcaggaact gtagctgaga gatcttcaga gctttttcca aggcgatatc 17580 actgggaaat aatagagaca aggttacaag ctagggctgt gttttcttct taaaatcttt 17640 agttcagttt ttttcaataa cagatttgta gtaggcatca ggtgactggg gattcgtatt 17700 cttcaag ttg aaatattacc ttgttgagaa agaaaccatg tgtgagacaa ccatgttgag 17760 aaagaaaaag tgattttata gaaaattaat attgatagtg agcattatat gaaaatcatg 17820 aagttagaac atatttggcc agaaaattta cattaatagt tacccatagc aattaatgca 17880 ttataattac acataccttt tctttaatga aaaagaattc tttccttcca aagttatgca 17940 tgctattgtt aaacattaga gaatatagag aagcaaaaaa gaaaatatct tttttgatat 18000 tttcttaaca tacgtctgtt cctaataatg tttatagttt agaagcattg catgaaatgg 18060 gtagatcaat tttctattta atgtttggat tcattaggta cgaagttagc aaattaattt 18120 ccattagggt gcc tgtatgg ttgtaaatcc tggacctgca gaagattttt cagtattggt 18180 ttgtagtctt ttgtttagca gcaaataatt agttctccag agcttctgaa attaattgac 18240 cactttaatg gtgtttacct acctagagaa agaaaaagaa cttctccaag tcccttggta 1830 0 aaattaagcc tcatgaacaa ttaactcaaa tatacacaag gcttgtcttt agcgagcata 18360 tactccctaa agttgattaa gctgaccaag tgattactgc ttataaattc accattttat 18420 ggagaagaag caaacactgc taaatacctt gtggaatcag aggaggggaa attagtaact 18480 tgaccccaat actgcgattt taaattgaat tcttgaagcc tacaagtttt acacaggact 18540 ttagagagct ggatagtatc actttgtcaa gtcctact tt tactatgatt ctttgagaaa 18600 aatacatctg actaaataac tctgaatcta aattggataa aataaatgg acattcaaaa 18660 tgttatttat gattttagaa aaatatcctt atagacacta gatgagtttt agtctcaaat 18720 caatcctccc tatcatagtc acttatcaaa ataactaaag caaagtggta gagctgtgct 18780 ctagaagttt gggatttatg atcacaatct tttccaatga gtcccctctt tcctctgcct 18840 gtcttcaaca tttgtttttt tttttttttg gttaggacta tccagattgt gtggcctatt 18900 tcaaactcat ggcaaataca ttggatgatc agaaattttc taatgtattt gaatttgtct 18960 acacaaacta gagtaattgc tattaatt cc tcaagtgtta attatttcat gcaaaaagga 19020 aaaaggctat tagtctttaa gtgtattagt atgtcaatat ttgggagaag tgtcatgcaa 19080 ttagtggttt gaatttccta tttatttta ttgcatttta ttttatttgc ctagtcaaat 19140 aaaaagta at gttaaataca tggaagcatg attgttttct acactaaaaa tcattttgac 19200 ttgaaaagat ctgatatcca tgaccttcat ctgaagtttt ggcagatgaa aatgtcagat aaatt ggaat ttttgtccta 19440 agaaatgaaa tttactatag tttcatctgt gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt 19500 ttaaaaaatc aagtgatagg gcttttcctc aataaaatct gaaatctctt atagttaagt 19560 gaacagaaca gtgtatctag gatgctag ac ttttttttca aagttagttt aaaacttata 19620 catagtaaaa tctgtatgcc ttagggatct ctgtttgcta tcccatagtg aatgattaat 19680 tagttctgt tagaaatagt cagaactagg ctgggtgtgg tggtggctca tgcctgtaat 19740 tccaggactt tgggaggcca aggcaggagg atctcttaag cccaggaatt tgcaaccagc 19800 ttgggcaggc tggtgagatc ctatctctac aaaaacaaac aaacaaacaa aggacaataa 19860 gaaagaaaga aatagccaga gctttgaaca aaatttctaa gtagaccaat gtaaaagtct 19920 gtcgtcaata tgtagtggct atgaatggag gttatgaatg aaagagaagg ataagatgaa 19980 ctagaggtga gaggggaaga cagcaggccc aagtgaaagg cagagcc gag tttatgctt 20040 tttggttatt ccaggtgtgt ctgctttgtc tcatgaaaca cctggatgat cactgatttc 20100 tagtggaaga ggtag gcatg 20280 gagaattctt tgatgggaca taattttctt cctttctttt tttttttttt tttttttttt 20340 tgagacggag ttttgctctt gttgcccagg ctggagtgca atggcacaat ctcggctcac 20400 tgcaacctcc gcctccca gg ttcaagcaat tctcccacct cagcctcccg cgtagctggg 20460 attacaggca tgtgccccca tgcctggcta attttttttg tatttttagt agagatgggg 20520 tttctccatg ttggtcaggc tggtctcgaa ctccttacct caggtgatcc acccacctcg 20580 gcctcccaaa gtgctgggat tacaggcgtg agccaccgcg cctggcctga tgggacatat 20640 ttttcattca atttattga tttaacctca caaaataaaa tatttcctta agatgactct 20 700 gtggtcattg ttgggcagca taagcttaat ggattttagt tatcataatt taccttaaac 20760 ccaatttgta tttcaggata taaatagagg tttattgtag tgaatcttcc aggaaatact 20820 aagtgatact aataattata gatggtgaac ttaagtcttt atattactga atttgtttgg 2 0880 tttgatgatg ctaggctatg gcattcttgc taatcaaaac gatgtgtcat ggtgtaacat 20940 aacttattaa aatgggcaca gataacacag gaagcttttt ataaaagcag ctcacaaatt 21000 gtgttacttt gaactgaact ggccatttt gggaaaggtc actgggttgt aaataaggac 21060 caaaagagtt acgtttatat tttttaaaag agattgagga gatttatttt tacatttctt 21120 gaaaatgcct tattttggta tggtattgac agatagtgaa attctgctca tttgtaaata 21180 tagtgtcata ttttaataat ttcaaacata ttgaaaatgc agaatttatt aatagtggga 21240 gcacattttc ctttttacta aatgttctac aggttctttt ctttccatcc acacacagtg 2 1300 ccattaccct cattctaagc ctttcaaaca tctggcagta agtgatctgc tgcacttagc 21360 tctttccagc tgagctgatt tttaaatttt cagaaaattt at tgcctgaa gtcaggggtt cgagaccaac ctgaccaaca 21600 tggagaaacc ctgtctctac taaaaatata aaaaaatagc cgggcatggt ggtgcatgcc 21660 tgtaatccca gctactcagg aggctgaggc aggagaattg cttgaaccca ggaggtggag 21720 gttgt ggtga gctgagattg cgccattgcg ctccagcctg ggcaacaaga gtgaaactct 21780 gtctcaaaaa aaaaaaaaaa aaaaaaaaag aaacaaaaaa aaaaaaaaaa caaaaagcaa 21840 acaaacaaaa aaacaaaaat tatcacttcc taattatttt gcattttact attatctatg 21900 ctattaacgt tatttgcctt cattgtattt gaaaggtgga ctatattcta ttgcactttc 21960 attgtactat attctaatat gcaactgtgt atccctt a acaccacta catgcagtct gctatctttt gttcttcctg ctttcaggct 22200 cctctcccag ctgtctgtct agcacaaccc agcataccaa attttcttaa atagggaaag 22260 ttgaacatgg taaaagaatg aatgaagtca aaagaatgtg gaaagaccta ggctttgcca 22320 tttagtaaag tttagcatct ctaagcctcc atctctttat caataaaatt gagcaatgat 22380 cccttttagt tctacccatt taagaagatt ttcaaatgaa aaccacaa cc tgctcatgtt 22440 tatgaaggca ctttggaaag cgctaaatac acgggttttt attagtagta aacacttact 22500 tcaccttttt cacttcttga ctttagttta caagggctca taatctaaat tatatcataa 22560 attgctgtcc cagatttttt tacagcctaa ttg ccacctg tatgttcgac tttccttctg 22620 ttctttatgt tagatactgg gatagtatgc accaggtggg tgtgccatca ctttctcaga 22680 tgatgtccac tgaagacctt gcatgatcat ggcattcatt ttcctgctgt attcagactg 22740 gcctcaacta ttttctttat tgctctccag gaaaaattac aaatgaatca gactgggcaa 22800 tgaagggtaa acctaattat cgctctttgt taaagacagc tcttgttaa a atgcggatat 22860 tgcaaattaa tggaaaaaat atgacatagt aaaccatact cacttattaa tatcttagta 22920 aggaataatt gatgaagtta cttaacctta gagccctaat tcagttaagt tttaatgaag 22980 gacaagttgt agagatatcg agaacccagg gcaggtgcct actga agaag ttccagacca 23040 aggaagtata aagaaggacc tgggtgggag cagtgagatt ggatatgagg gccactggca 23100 aagttttgcc ccagaacagt gtcaaaatgt ttgcatttgg catagccctt tctctttttg 23160 ttctgaatgg ctttgctaga atatcttttc tataatgaat ttatcctgct tctcagatat 23220 tgctaaagca ctcccttttg aattttggtg ctttaacatg cattttgata cat taccaaa 23280 taaggtctga atgacacaaa ttttagaact ctccagagaa aagaaagatg ctgagggaaa 23340 aagcataggt ttgggactca ctaaatccca gttcaattcc tttctttaat aaatatattc 23400 aattttacct gagaaagctc tcgtgctctc gaattttatt taga aatttc tctttgtaca 23460 tgattgattt cacaatcctt cttctgcctc ctcttctact ttcttctttc tagattttcc 23520 tatctttatg aagattattc tgccttatcc tcaacagtta gaaacaatat ttttgaaaat 23580 cactacggta tcctgcatag tgatttccca tgccaacttt actaatttcc attataaatt 23640 attatttatt gatgcctaga gggcagatga gtgtagctgc tatggagtga ggagacaaaa 23700 cata agaaag ttatgatcct accctcaggt aatgattcag acatgataat taagtcaaca 23760 aattgataga aactaatcac taactctctg gctatagtca ttctttcaat gaatagctca 23820 ttactgagta tgcatgctac agtaacaaaa ttatataagg ctgttgatta aatgttgatt 23880 a agtgcatgt cttattcaga gtttttttat atttgaaatg gaagaggctg gacttcagta 23940 atttgctata aactgctagt atatgattat ttgggggcag ttatttttta aagaataatt 24000 taaatatgga atgtttagca gtttgttttt tccctgggaa aaaccatact attattccct 24060 cccaatccct ttgacaaagt gacagtcaca ttagttcaga gatattgatg ttttatacag 24120 gtgtagcctg taagaga tga agcctggtat ttatagaaat tgacttattt tattctcata 24180 tttacatgtg cataattttc catatgccag aaaagttgaa tagtatcaga ttccaaatct 24240 gtatggagac caatcaagt gaatatctgt tcctcctctc tttattttag ctggaccaga 24300 ccaattttga ggaaaggata cagacagcgc ctggaattgt cagacatata ccaaatccct 24360 tctgttgatt ctgctgacaa tctatctgaa aaattggaaa ggtatgttca tgtacattgt 24420 ttagttgaag agagaaattc atattattaa ttatttagag aagagaaagc aaacatatta 24480 taagtttaat tctttatattt aaaaatagga gccaagtatg gtggctaatg cctgtaatcc 24540 caactatttg ggaggccaag atgagaggat tgcttgagac caggagtttg ataccagcct 24600 gggcaacata gcaagatgtt atctctacac aaaataaaaa agttagctgg gaatggtagt 24660 gcatgcttgt attcccagct actcaggagg ctgaagcagg agggttactt gagcccagga 24720 gtttgaggtt gcagtgagct atgattgtgc cactgcactc cagcttgggt gacacagcaa 24780 aaccctctct ctctaaaaaa aaaaaaaaaa aggaacatct cattttcaca ctgaaatgtt 24840 gactgaaatc attaaacaat aaaatcataa aagaaaata atcagtttcc taagaaatga 24900 ttttttttcc tgaaaaatac acatttggtt tcagagaatt tgtcttatta gagaccatga 24960 gatggatttt gtgaaaacta aagtaacacc attatga agt aaatcgtgta tatttgcttt 25020 caaaaccttt atatttgaat acaaatgtac tccctgggaa gtcttaaggt aatggctact 25080 ggttatcaaa caaatgtaaa aattgtatat ttttgagtac ctgttacatg ccaggtagaa 25140 tatctcctct cagccactct gagtggaaag catcattatc tctattttac agaaaagcaa 25200 actgaggctc agagagataa tatactttgc cagttaatga atgatggagc catgattcca at gaagcctg aactatgtga 25440 agacctaggt ggagaactgg ccttaggaac tcaatgggac caaggactca aatgccacct 25500 ggtggcattt gccttatgct ggttttattt tctcagaccg gaccagcttt ctacataaag 25560 tgggtccctg gttagaactc tttgctccta tctttaagga ccacgaaaga aggagccctt 25620 tgtccttggc taaatgtgaa aaatcccaga gactcttgag tcatagtgct taccccttgg 25680 gccactcata gtctagaatg aactaggctg agtctcgtgc caacagcaca ggcctgatgc 25740 cagataaaag ggtgagtgaa gggggataaa aaataagaca tagctactaa attattgcac 25800 caagtaaaa acattgagtt gacttgcaat ttgtttcttt taattaatt catttcct tt 25860 ttttggcatt ttgaaggcaa agtaagatat taaactttat tttattgat tttattcaaa 25920 gaattaagct agtgggagta gcagattcac acttctaaga tcaagggcca gcttctatta 25980 ttgaacactt ggtgtgtgca aatgccatga taggg ata ctttgttttg ttttttattt 26040 tttattgggt tcgatctctt ttgtttatga tgtatcccca agtgcctaga atagggcctg 26100 gcatatggta tatactcaat aaatatttgt tgaatgaatc catgatggaa tgtgaaatgg 26160 ctagcattac atagaaacct gtagcattgc tggagagata aaatatataa acataatcca 26220 ttgcaggtat attgacaagt tcaaaataat ataatgggta ttgaatatct aaatgtttgt 2628 0 tgttgttgtt gctgttgttt ttgagacaga gtcttgctct gttgcccagg ctggagtgta 26340 atggtgcaat tttggctcac tgcaaacttc gtctcctggg ttcaagtgat tctcctgcct 26400 cagcctctcg agtagctggg tttacaggca ctc gccacaa tgcctggcta atttttgtat 26460 tttagtagat gtggagtttc gccatgttgg ccaggctggt cttgaactcc tgacctcaag 26520 tgatctgccc accttggcct cccaaaatgc tgggattata ggtgtgagcc actatgccca 26580 gctttgaata tctaagtttt aattggatgc tgagggaatg attaatcaga gtagggctgg 26640 gttaattgaa aaatgtgata catttgtatt tatggccaga tagagaacat gaatctgaat 26700 ttgcagaatt atct ggctta acattttttt ctttccagtt ttcactgtat cccccatgtt 26760 gattcaattt aaaaaatata cctattttac ttcaattcaa caatgctatg ccagtacaaa 26820 cccatacgtt ctattatttt tgttttgttt tgtttttgta tctccaccct gttacttctt 26880 ttcttataaa attggtattt gaaatttatt gaaatatttt ggaagagtga cataccattt 26940 ttggtacttt gtacctctgc acccttggga agtgaccctg gcttcacatt tcataactgc 27000 cttgtgacca tggccctcaa gtggttgcca gatggttgaa gaacattaac ctatctggct 27060 caattttgtg accatggatt gaatcctcta cataactgca gtgtgcaaac cacacatccg 27120 ttccaagatt gtagtca gga tatgaacttt ttaagaataa aacttcttcc cttctgatct 27180 gggcctggta tgtggtccta ctagaaccac atcacctact cttggtgcta acaatttgtg 27240 gcaccaagtt gttcaagttt cacccattaa agaaattccc cgaccttgcc ttctcctcag 27300 gtaactaccc cattctattt tttctttcat agctaacatt ctctgctctc ctggtctctc 27360 tacttcactt tcatttacat ctcagctcct gaagtatggt ttcc accatg ttcctaaaac 27420 tacattgccc agggtcacta gagacctctt atgaaatata acaacacctt tctacattac 27480 ttcc gtgtgg accacttttt cacattgaac ccattttgtt ggtttatgta cacacccctt 27540 ccttggcttt cccatctgat ccatttctcc t ttgatggag aaggtgagtc tgctccatat 27600 ttagcttctt actctgagta accaaatgtt atggatggga ggttagctct gtgtgtgaga 27660 gaaaggtgga gaagcatgtg gggagggaaa tagatgggaa aaggtaatta ggctttatag 27720 aagggctctc attagcaagc ttctagggga tgccaagatc catgcttaga gattgccagg 27780 cttgtcttca aatctcagct gtgtattact cctttatgtt ttttgtttgt ttgtgttgtt 27 840 tgtttttgag acagagtctc gctgtgtcac ccaggctgga gtgtagtggt gtgatctcag 27900 ctcactgcaa actctgcctc ctgggttcaa gcgaatctca gtctcctgag tagctgggac 27960 tacaggcatg caccaccagg cctggctaat ttttgtagag acggggtt tt gctatgctgg 28020 ccaggctggt cttgaactcc tgacctcaag tgatctgccc gccttggcct cccaaagtgt 28080 tgggattagt ggcgtgagcc actgccccgg cctattactc ctttagagtg atttagagcc 28140 atgtttactt atggtaactt gacagtaatg ggaataacca ctgatgaaac gtaaagcctt 28200 tgtctaattg tttacctagt tcttccttgt ggttcatgaa atttttcatc tctgtacagt 28260 ttgaaaatt a agatgataat atttagagat atttattcc tttgtgaaga gaaaaaaggc 28320 tttcattaac agaaatcagt ggcaataact taataaatac aatcagctgg tgttcctata 28380 gtatttaaaa gaaaacagaa agttactag atttcagcca gttttcagac tatttaatgt 2 8440 ctattcttac tataatagaa aatatataat ttgatcttgt tctcattttt caaagacctt 28500 taatacatga ttttagtagt tgaaaatgaa gtttaatgat agtttatgcc tctactttta 28560 aaaacaaagt ctaacagatt tttctcatgt taaatcacag aaaaagccac ctgacatttt 28620 aacttgtttt tgatttgaca gtgaaatctt ataaatctgc cacagttcta aaccaataaa 28680 gatcaaggta ta agggaaaa atgtagaatg tttgtgtgtt tattttttcc accttgttct 28740 aagcacagca atgagcattc gtaaaagcct tactttattt gtccaccctt ttcattgttt 28800 tttagaagcc caacactttt ctttaaca tacaatgtgg ccttttcatg aaatcaattc 28860 cctgcacagt gatatatggc agagcattga attctgccaa atatctggct gagtgtttgg 28920 tgttgtatgg tctccatgag attttgtctc tataatactt gggttaatct ccttggatat 28980 acttgtgtga atcaaactat gttaagggaa ataggacaac taaaatattt gcacatgcaa 29040 cttattggtc ccacttttta ttcttttgca gagaatggga tagagagctg gcttcaaaga 29100 aaaatcctaa actcattaat gcccttcggc gatgtt tttt ctggagattt atgttctatg 29160 gaatcttttt atatttaggg gtaaggatct catttgtaca ttcattatgt atcacataac 29220 tatattcatt tttgtgatta tgaaaagact acgaaatctg gtgaataggt gtaaaaatat 29280 aaaggatgaa tccaactcca aacact aaga aaccacctaa aactctagta aggataagta 29340 aaaatccttt ggaactaaaa tgtcctggaa cacgggtggc aatttacaat ctcaatgggc 29400 tcagcaaaat aaattgcttg cttaaaaaat tatttctgt tatgattcca aatcacatta 29460 tcttactagt acatgagatt actggtgcct ttattttgct gtattcaaca ggagagtgtc 29520 aggagacaat gtcagcagaa ttaggtcaaa tgcagctaat tacatatatg aatgtttgta 29580 atattttgaa atcatatctg catggtgaat tgtttcaaag aaaaacacta aaaatttaaa 29640 gtatagcagc tttaaatact aaataaataa tactaaaaat ttaaagttct cttgcaatat 29700 attttcttaa ta tcttacat ctcatcagtg tgaaaagttg cacacctgaa aatccaggct 29760 ttgtggtgtt taagtgcctt gtatgttccc cagttgctgt ccaatgtgac tctgatttat 29820 tattttctac atcatgaaag cattatttga atccttggtt gtaacctata aaaggagaca 29880 gattcaagac ttgtttaatc ttcttgttaa agctgtgcac aatatttgct ttggggcgtt 29940 tacttatcat atggattgac ttgtgtttat attggtcttt atgcc tcagg gagttaaaca 30000 gtgtctccca gagaaatgcc atttgtgtta cattgcttga aaaatttcag ttcatacacc 30060 cccatgaaaa atacatttaa aacttatctt aacaaagatg agtacactta ggcccagaat 30120 gttctctaat gctcttgata atttcctaga agaaatttt t ctgacttttg aaataataga 30180 tccataatat atattcttat ggaaatctga aaccatttgg gcatttgggg gtaaaaagta 30240 ttttattagt aaatttaaat gaggtagctg gataattaaa ttacttttaa gttacctttg 30300 agatgatttt tctcaatcag agcaccaccc agagctttga gaaacaattt tattcacagc 30360 ttctgattct atttgatgta atttttagaa aataagtttt gctggttg ct ttgaatcagg 30420 gtatggagta cagttcactc tgatcctatc atataaatca tgtaagtata taacattttc 30480 aataagtgat tgttggattg aagtgaatga tatttcaagt aattgttatg tcatggccaa 30540 gatttcagtg aaactcaaaa tttctcc tgg ttgtgttctc cattgcatgc tgcttctatt 30600 gattaaccta agcactactg agtagaagct ggaagagggg tctaattaga aggccccttt 30660 ctatgctctg cttggcttgt aaaataattt atttctctag atcccaccaa catagtagtt 30720 tcatgtatgc aaaaacaccc acctaaatgt caaagtttgt atgatacatg gacatatcta 30780 tagaattttt tttggtctgg tgcatgccaa aaaataaaca tgatatagaa gaatttaata 3 0840 tttattgagt acctaatctg ttccagttca atatgaaggt ctttatgcag attattttac 30900 ttaattttcc tagtaactcc atggagcaaa aattatctct aatttata acaggaagtt 30960 gagcgtgagg caaattaagt aactttccca aagttacaca tatggtaagt ttgagagata 31020 tcccagtctc tttagctcca aagcctttga ccctttcacc ataccagatt atgattgcta 31080 ttaatatata attataatta taatgattgt atttaggtac tcaacagaat ggtgactcta 31140 gtaaccagcc ttggttctgc tgagcttctc tgcgtcttct caggagacac aggctacaga 31200 gcttgaaggc tgaggattct tccagggtca cttcaggggc aaatctgaaa ctttcttcag 31 260 gacaggaatc aacgagatct tctcacttac ttatacctgg gggaggaact gtatgaaatc 31320 cacccaagaa ccagtcatgc taagggccaa acctatagac aaaaaaaggg ataggagaat 31380 ggaggtatgta tggagaaaga ctaaattgtt cttaaacttc tcaagcttaa aaatatcc ca 31440 gcaaaagaga tcgtaaaagc ccttcatggc gtattaatta tccatgcatg ggggtgagtg 31500 gaaaggtact cctgagcccg aggctacagc tttggaacta gcagcacctt tgaaggggaa 31560 agcgtgtttc catcatctca actcctactg ataaccaatg gaatattggt gagtaaagga 31620 tcctggggga agaagcagct gaaatgtgta ggtgagaagg cagagagaag aatatttata 31680 ttgggaatgg cacaag tgg atgaggctgc aggtttttca cccttgtcat agagaaaaaa 31740 ccacgctgac accatgcagt tttaaatagt gagaaatttg caaattgtta gatcttaaat 31800 aatttagata aacatagtgg ccatttagat tattgcagtt ttttcaggat atctgatctc 31860 tt gatttcat tctttttgtc tcttataaga ataaaagggg gggagaaaat ttagccatta 31920 tagtatttct ctacattttc tctgtccttt tacataactt acaccagtgc cttcctattt 31980 atggtattat ttatgggtat ttcttctttt ctttcactga gcaaggataa atgagccagg 32040 gattcttgaa actactgtaa cacttctctt agaaatagat ggtcatactt tcagaatctc 32100 tacacattct tagtccctct aaacaatga t agttgtggca taaaaatatt tgcttggttt 32160 caggactgat agagaaaagt actataaaat ttgctgttaa ctgtgaaagg ttaaaaaaaa 32220 ggaggtgcca tcatgaagga gctaatcttt ctgaagtact gctgtagttt taaatattat 32280 tagctat gac ttctcaccat taactatgca cttgcttttt cttcatctga ctcagcagcc 32340 agatagatgc aacattgtct ttaacattta agactcctag caagtccggg cacgggggct 32400 cacacctgta atcccagcac tttgggaggc cgaggtgggc aaatcacaag gtcaggagtt 32460 tgagaccagc ctggccaata tggtgaaacc ctgtctctac taaaagtaca aaaatcagcc 32520 aggtgtggtg gcgtggtggc gggcacc tgt ggtcccagct acttgggagg ctgaggcagg 32580 agaatagctt gaacctggga ggcagaggtt gcagtgagct gagatcgcac cactgcactc 32640 cagcctgggt gacagagcga gactccatct caaaaaaaaa aaaaaaaaaa aagactccta 32700g 327 01 <210> 52 <211> 1060 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="nAPG00969" <400> 52 Met Lys Gln Thr Ser Tyr Ser Leu Gly Leu Ala Ile Gly Ile Ala Ser 1 5 10 15 Val Gly Tyr Gly Leu Ile Asp Asn Asp Glu Asn Ile Val Asp Ala Gly 20 25 30 Val Arg Leu Phe Pro Glu Ala Asn Ser Lys Asn Asn Asp Gly Arg Arg 35 40 45 Lys Ser Arg Gly Ser Lys Arg Leu Ile Arg Arg Lys Arg His Arg Ile 50 55 60 Ala Arg Val Lys His Leu Leu Lys Glu Ser Gly Ile Asp Val Ser Tyr 65 70 75 80 Glu Asn Thr Val Leu Thr Asn Pro Tyr Glu Ile Arg Cys Lys Gly Leu 85 90 95 Thr Leu Pro Leu Thr Asn His Glu Leu Ser Ile Ala Leu Leu His Leu 100 105 110 Ala Lys Arg Arg Gly Val His Asn Val Lys Ser Met Asp Gln Glu Lys 115 120 125 Val Lys Gly Asn Glu Leu Ser Thr Lys Glu Gln Leu Thr Ile Asn Asp 130 135 140 Asn Leu Leu Glu Glu Lys Phe Ile Cys Glu Leu Gln Leu Glu Arg Leu 145 150 155 160 Asn Lys Glu Gly Ile Val Arg Ser His Ser Asn Arg Phe Lys Thr Ala 165 170 175 Asp Tyr Ile Lys Glu Ile Lys Asn Leu Leu Glu Thr Gln Ala Lys Gln 180 185 190 Asn Thr Leu Val Thr Glu Glu Phe Ile Glu Lys Tyr Ile Glu Ile Phe 195 200 205 Ser Gly Arg Arg Lys Tyr Tyr Glu Gly Pro Gly Gly Glu Ser Lys Tyr 210 215 220 Gly Trp Lys Gly Asp Ile Glu Lys Trp Tyr Glu Gly Leu Met Gly Lys 225 230 235 240 Cys Thr Tyr Phe Pro Lys Glu Leu Arg Cys Val Lys His Ala Tyr Ser 245 250 255 Ala Ala Leu Phe Asn Leu Leu Asn Asp Leu Asn Asn Leu Ser Ile Asn 260 265 270 Arg Glu Glu Asp Thr Lys Leu Ser Gln Tyr Glu Lys Glu Gln Ile Ile 275 280 285 Glu Lys Ile Phe Lys Val Arg Lys Thr Pro Thr Leu Thr Gln Ile Ala 290 295 300 Lys Leu Leu Lys Val Asp Pro Thr Asn Ile Lys Gly Phe Arg Thr Lys 305 310 315 320 Ala Asn Gly Thr Pro Asp Phe Leu Ser Ile Lys Ile Tyr His Asp Leu 325 330 335 Lys Gly Ile Ile Asp Asp Lys Gln Leu Leu Asp Asp Ile Ala Phe Leu 340 345 350 Asp Asn Val Ala Gln Ile Leu Thr Val Trp Gln Asp Ser Gln Ser Ile 355 360 365 Gln Glu Lys Leu Lys Thr Leu Asn Lys Asn Leu Asp Asp Lys Thr Ile 370 375 380 Lys Glu Ile Ser Glu Leu Lys Lys Tyr Thr Gln Thr His Ser Leu Ser 385 390 395 400 Leu Lys Leu Ile Asn Val Leu Leu Pro Glu Leu Trp Glu Thr Thr Lys 405 410 415 Asn Gln Met Thr Ile Leu Ser Glu Leu Lys Leu Lys Pro Arg Lys Ile 420 425 430 Asp Leu His Asn Cys Asn Glu Ile Pro Val Asn Met Ile Asn Asp Leu 435 440 445 Ile Val Ser Pro Val Val Arg Arg Ser Leu Thr Gln Ser Ile Glu Met 450 455 460 Ile Asn Gln Ile Ile Lys Asp Tyr Gly His Pro Arg Glu Ile Val Ile 465 470 475 480 Glu Leu Ala Arg Glu Lys Asn Ser Glu Glu Lys Lys Asn Phe Ile Lys 485 490 495 Ser Leu Asn Glu Lys Asn Lys Gln Ile Asn Asp Glu Val Ile Glu Lys 500 505 510 Leu Asn Ala Ser Asn His Arg Asp Asn Lys Gly Met Phe Asn Lys Val 515 520 525 Lys Leu Trp Ile Leu Gln Asp Gly His Cys Leu Tyr Ser Leu Lys Pro 530 535 540 Ile Arg Leu Glu Asp Leu Leu Asn Asn Pro Asn His Tyr Glu Ile Asp 545 550 555 560 His Ile Ile Pro Lys Ser Val Ser Phe Asp Asp Ser Met Ser Asn Lys 565 570 575 Val Leu Val Tyr Gln Ile Glu Asn Ser Lys Lys Gly Asn Arg Thr Pro 580 585 590 Tyr Gln Tyr Leu Thr Ser Ala Asp Lys Thr Ile Thr Tyr Glu Lys Phe 595 600 605 Lys Ala Asn Ile Thr Gln Leu Ala Lys Ser Asn His Lys Ile Ser Lys 610 615 620 Lys Lys Leu Asp Tyr Leu Leu Glu Glu Arg Asp Ile Asn Arg Phe His 625 630 635 640 Ile Lys Lys Glu Phe Ile Asn Arg Asn Leu Val Asp Thr Arg Tyr Ala 645 650 655 Thr Arg Ser Leu Ile Asn Leu Leu Lys Tyr Tyr Phe Ser Glu Lys Asp 660 665 670 Ile Asn Val Lys Val Lys Ser Ile Asn Gly Ser Phe Thr Asp Tyr Leu 675 680 685 Arg Lys Leu Trp Asn Phe Pro Lys Asp Arg Glu Phe Tyr His Lys His 690 695 700 His Ala Glu Asp Ala Leu Ile Ile Ala Met Ala Asn Lys Ile Phe Thr 705 710 715 720 Thr Arg Lys Ile Phe Lys Glu Gln Asn Ser Val Phe Ser Asp Glu Gln 725 730 735 Ile Leu Asp Gly Glu Val Thr Asn Ile Leu Ser Asp Asp Gln Phe Gln 740 745 750 Ala Glu Phe Thr Glu Lys Phe Tyr Lys Val Gln Ala Ile Lys Lys Tyr 755 760 765 Asp Lys Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro Asn Arg Gln 770 775 780 Leu Phe Asp Asp Thr Leu Tyr Ser Thr Arg Glu Phe Glu Gly Glu Glu 785 790 795 800 Tyr Tyr Ile Gly Lys Ile Lys Asp Ile Tyr Asn Leu Lys Asp Lys Arg 805 810 815 Leu Lys Lys Ile Phe Thr Lys Ser Pro Glu Lys Ile Leu Met Tyr Gln 820 825 830 His Asp Ser Gln Thr Phe Lys Lys Leu Lys Gln Ile Met Arg Ser Tyr 835 840 845 Glu Asp Glu Val Asn Pro Leu Ala Lys Tyr His Lys Glu Thr Gly Glu 850 855 860 Tyr Leu Arg Lys Glu Cys Lys Lys Gly Asn Gly Pro Ile Val Lys Ser 865 870 875 880 Leu Lys Tyr Arg Val Thr Lys Leu Gly Val His Lys Asp Ile Thr His 885 890 895 Lys Tyr Glu Asn Ser Lys Asn Lys Val Val Ile Leu Ser Leu Lys Pro 900 905 910 Phe Arg Met Asp Val Phe Lys Glu Asn Gly Val Tyr Lys Phe Ile Thr 915 920 925 Ile Arg Tyr Cys Asp Leu Lys Glu Thr Val Asn Ser Tyr Thr Ile Ser 930 935 940 Glu His Leu Tyr Lys Ala Lys Leu Lys Ala Lys Asp Ile Lys Ser Met 945 950 955 960 Asp Ser Phe Lys Trp Ser Phe Tyr Lys Asn Asp Leu Leu Glu Tyr Asn 965 970 975 Gly Glu Leu Cys Thr Phe Lys Gly Val Asn Asp Asp Lys Lys Asn Lys 980 985 990 Ile Glu Val Asn Trp Val Glu Lys Asn Phe Ala Ile Tyr Ala Glu Lys 995 1000 1005 Lys Asn Leu Lys Ser Lys Gln Leu Val Lys Ser Ile Thr Lys Ser 1010 1015 1020 Thr Val Lys Ser Leu Leu Lys Tyr Thr Thr Asp Ile Leu Gly Asn 1025 1030 1035 Arg Tyr Pro Val Arg Asn Glu Lys Leu Lys Leu Met Ile Arg Lys 1040 1045 1050 Gln Thr Phe Arg Gly Asp Leu 1055 1060 <210> 53 <211> 1092 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="nAPG06646" <400> 53 Met Arg Tyr Ser Ile Gly Leu Ala Ile Gly Thr Thr Ser Ile Gly Asn 1 5 10 15 Ala Val Ile Asn Lys Asp Leu Gln Arg Phe Glu His Leu Gly Val Arg 20 25 30 Ile Phe Asp Ala Ala Glu Asn Pro Lys Asp Gly Ser Ser Leu Ser Ala 35 40 45 Pro Arg Arg Leu Ala Arg Ser Ser Arg Arg Arg Leu Arg Arg Arg Lys 50 55 60 His Arg Val Glu Arg Thr Lys Gln Leu Leu Ile Asn Lys Gly Leu Leu 65 70 75 80 Thr Lys Thr Gln Val Lys Asn Leu Tyr Asn Ser Lys Asn Ile Asn Leu 85 90 95 Asp Ile Trp Asp Ile Arg Val Ser Gly Ile Asp Arg Lys Leu Phe Asn 100 105 110 Asn Glu Phe Ala Arg Val Leu Ile His Phe Ser Lys Asn Arg Gly Phe 115 120 125 Lys Ser Asn Arg Lys Ser Glu Leu Lys Glu Asp Asp Asn Gly Ala Ile 130 135 140 Leu Ser Ala Val Lys Glu Asn Arg Glu Leu Met Asp Glu Lys Gly Tyr 145 150 155 160 Arg Thr Ile Ala Glu Met Leu Val Ser Asp Glu Lys Tyr Glu Gly Thr 165 170 175 Lys Arg Asn Lys Gly Gly Asp Tyr Ser His Val Val Ala Arg Ser Asp 180 185 190 Ile Glu Asn Glu Ile Cys Leu Leu Phe Gln Lys Gln Arg Glu Tyr Gly 195 200 205 His Pro Phe Ala Thr Glu Glu Asn Glu Glu Ala Phe Leu Ser Ile Trp 210 215 220 Ser Ser Gln Arg Pro Phe Ser Thr Lys Asp Asp Ile Val Lys Lys Ile 225 230 235 240 Gly Asn Cys Thr Leu Glu Pro Lys Glu Lys Arg Ala Pro Lys Ser Thr 245 250 255 Tyr Thr Phe Glu Arg Phe Arg Ala Leu Asp Lys Leu Asn Arg Leu Arg 260 265 270 Ile Leu Ser Thr Thr Ala Pro Ser Arg Pro Leu Thr Asn Glu Glu Arg 275 280 285 Lys Ser Ile Leu Ser Ser Leu Phe Ser Lys Lys Glu Val Lys Tyr Lys 290 295 300 Glu Leu Arg Lys Leu Leu Lys Leu Thr Asp Asp Gln Arg Phe Asn Glu 305 310 315 320 Ile Tyr Tyr Ser Pro Asp Glu Thr Ile Glu Lys Thr Glu Asn Arg Thr 325 330 335 Phe Leu Ser Leu Glu Ser Gln Tyr Lys Ile Lys Lys Ile Ile Glu Lys 340 345 350 Thr Glu Ser Lys Asn Met Gln Ser Ser Tyr His Pro Ile Asp Tyr Asp 355 360 365 Thr Ile Gly Tyr Ala Leu Thr Val Phe Lys Asp Asp Lys Asp Ile Gln 370 375 380 His Tyr Leu Gln Asn Ser Tyr Ile Asp Ser Lys Gly Lys Ala Ile Pro 385 390 395 400 Asn Met Ala Asn Arg Glu Tyr Asn Leu Glu Leu Ile Glu Glu Leu Leu 405 410 415 Gly Leu Ser Phe Ala Lys Phe Gly His Leu Ser Leu Lys Ala Leu Asn 420 425 430 Asn Ile Leu Pro Tyr Met Glu Glu Gly Glu Pro Tyr His Ile Ala Cys 435 440 445 Glu Met Ala Ser Tyr Gln Phe Ser Gln Arg Leu Ser Lys Glu Lys His 450 455 460 Arg Leu Leu Pro Pro Ile Pro Val Asp Glu Ile Pro Asn Pro Val Val 465 470 475 480 Val Arg Ala Leu Thr Gln Val Arg Lys Val Leu Asn Ser Ile Ile Lys 485 490 495 Lys Tyr Gly Pro Pro Ser Asp Ile Tyr Ile Glu Leu Ala Arg Glu Met 500 505 510 Ser Lys Pro Phe Lys Glu Arg Lys Ser Leu Glu Arg Glu Phe Asn Glu 515 520 525 Asn Arg Gln Ile Asn Glu Lys Ala Lys Ala His Ile Ser Glu Leu Tyr 530 535 540 Arg Ile Pro Asn Asp Pro Arg Pro His Asp Ile Leu Lys Phe Lys Leu 545 550 555 560 Trp Asn Glu Gln Asn Gly Ile Cys Pro Tyr Ser Leu Lys Pro Ile Ser 565 570 575 Ile Glu Tyr Leu Phe Asn Ile Gly Tyr Ala Glu Val Asp His Ile Ile 580 585 590 Pro Tyr Ser Arg Ser Phe Asp Asp Ser Asn Gly Asn Lys Val Leu Val 595 600 605 Leu Thr Arg Glu Asn Gln Asn Lys Leu Asn Arg Thr Pro Tyr Glu Trp 610 615 620 Phe Gly His Glu Glu Asn Arg Trp Glu Asp Phe Val Ser Phe Ile Arg 625 630 635 640 Thr Met Lys Val Gly Lys Lys Lys Lys Asn Met Leu Leu Lys Lys Asn 645 650 655 Phe Asp Glu Glu Gln Glu Glu Gln Ile Leu Ser Arg Asn Leu Asn Asp 660 665 670 Thr Arg Tyr Ile Thr Arg Tyr Ile Lys Ser Phe Ile Glu Asp Asn Leu 675 680 685 Glu Phe Arg Thr Glu Glu Asn Lys Glu Gln Tyr Val His Thr Val Asn 690 695 700 Gly Ala Tyr Thr Ser Leu Met Arg Lys Arg Trp Gly Leu Asn Lys Asp 705 710 715 720 Arg Arg Gly Asn Asp Leu His His Ala Val Asp Ala Ala Ile Ile Ala 725 730 735 Val Ser Leu Pro Phe Lys Asn Lys Val Asn Ala Tyr Phe Lys Arg Gln 740 745 750 Glu Thr Gly Leu Ser Lys Leu Leu Asn Asn Lys Lys Asp Ile Phe Pro 755 760 765 Glu Pro Trp Arg Asn Phe Ile Lys Glu Leu Glu Ala Arg Met Ile Gln 770 775 780 Asp Pro Glu Lys Met Lys Arg Ala Leu Glu Ser Leu Glu Leu Glu Thr 785 790 795 800 Tyr Gly Glu Ile Phe Leu Asn Lys Leu Lys Pro Ile Phe Val Ser Arg 805 810 815 Met Pro Lys His Ser Ile Lys Gly Gln Ile His Glu Glu Thr Ile Arg 820 825 830 Arg Val Arg Gly Phe Thr Glu Glu Gly Phe Leu Val Thr Val Lys Lys 835 840 845 Thr Arg Leu Asp Gln Ile Pro Phe Asp Lys Asn Gly Asp Phe Pro Met 850 855 860 Tyr Gly Lys Glu Thr Asp Ile Lys Thr Tyr Met Ala Ile Lys Gln Arg 865 870 875 880 Tyr Leu Glu Tyr Gly Gln Asp Lys Gln Lys Ala Phe Ala Val Pro Leu 885 890 895 Arg Lys Pro Ser Lys Asn Pro Lys Asn Ala Pro Ile Val Arg Ser Val 900 905 910 Lys Ile Glu Gly Lys Ala Asn Arg Val Val Met Leu Asp Asp Lys Ala 915 920 925 Ala Ala Asp Asn Ala Ser Ile Val Arg Thr Glu Val Phe Arg His Lys 930 935 940 Lys Thr Gly Glu Tyr Tyr Leu Thr Pro Val Tyr Val Ala Asp Ile Leu 945 950 955 960 Ser Asn Lys Ile Pro Asp Arg Leu Ile Thr Ile Lys Lys Ser Tyr Ser 965 970 975 Asp Trp Asp Arg Ile Thr Asp Glu His Glu Tyr Leu Phe Ser Leu Tyr 980 985 990 Asn Asn Asp Leu Val Lys Ile Ile Leu Pro Lys Glu Lys Glu Thr Lys 995 1000 1005 Lys Tyr Thr Gly Gly Asn His Leu Trp Gln Glu Gly Phe Phe Tyr 1010 1015 1020 Phe Lys Gly Val Asp Ser Ser Asn Ala Gly Ile Lys Ile Ile Asn 1025 1030 1035 His Leu Asn Ser Phe Glu Ala Arg Ile Gly Thr Lys Arg Leu Ile 1040 1045 1050 Ala Phe Glu Lys Tyr Gln Val Asn Pro Leu Gly Glu Ile Asn Lys 1055 1060 1065 Val His Gly Glu Lys Arg Pro Gly Glu Leu Leu Asn Lys Glu Glu 1070 1075 1080 Ile Lys Glu Asn Arg Lys Asn Ile Ser 1085 1090 <210> 54 <211> 1108 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="nAPG09748" <400> 54 Met Ala Ile Arg Ser Ile Lys Leu Lys Leu Lys Thr Arg Thr Gly Pro 1 5 10 15 Glu Ala Gln Asn Leu Arg Lys Gly Ile Trp Arg Thr His Arg Leu Leu 20 25 30 Asn Glu Gly Val Ala Tyr Tyr Met Lys Met Leu Leu Leu Phe Arg Gln 35 40 45 Glu Ser Thr Gly Gly Gln Thr Lys Lys Glu Leu Gln Glu Glu Leu Val 50 55 60 Arg His Ile Arg Glu Gln Gln Gln Lys Asn Arg Ala Asp Lys Asn Thr 65 70 75 80 Gln Ala Leu Pro Leu Asp Lys Ala Phe Ala Ala Leu Arg Gln Leu Tyr 85 90 95 Glu Leu Leu Val Pro Ser Ser Ile Gly Gln Ser Gly Asp Ala Gln Ile 100 105 110 Ile Ser Arg Lys Phe Leu Ser Pro Leu Val Asp Pro Asn Ser Glu Gly 115 120 125 Gly Lys Gly Thr Ser Lys Ala Gly Ala Lys Pro Thr Trp Gln Lys Lys 130 135 140 Lys Glu Ala Asn Asp Pro Thr Trp Glu Gln Asp Tyr Glu Lys Trp Lys 145 150 155 160 Lys Arg Arg Glu Glu Asp Pro Thr Ala Ser Val Ile Thr Thr Leu Glu 165 170 175 Glu Tyr Gly Ile Arg Pro Ile Phe Pro Leu Tyr Thr Asn Thr Val Ala 180 185 190 Asp Ile Ala Trp Leu Pro Leu Gln Ser Asn Gln Phe Val Arg Thr Trp 195 200 205 Asp Arg Asp Met Leu Gln Gln Ala Ile Glu Arg Leu Leu Ser Trp Glu 210 215 220 Ser Trp Asn Lys Arg Val Gln Glu Glu Tyr Ser Lys Leu Gln Glu Lys 225 230 235 240 Met Thr Gln Leu Asn Glu Gln Leu Glu Gly Gly Gln Glu Trp Ile Ser 245 250 255 Leu Leu Glu Gln Tyr Glu Glu Gln Arg Glu Gln Glu Leu Ile Glu Asn 260 265 270 Met Thr Ala Ala Asn Asp Lys Tyr Arg Ile Thr Lys Arg Gln Met Lys 275 280 285 Gly Trp Asn Glu Leu Tyr Glu Gln Trp Ser Thr Val Leu Pro Asn Ala 290 295 300 Ser His Glu Gln Tyr Arg Glu Ala Leu Lys Arg Val Gln Gln Arg Leu 305 310 315 320 Arg Gly Arg Phe Gly Asp Ala His Phe Phe Gln Tyr Leu Met Lys Glu 325 330 335 Glu His His Leu Ile Trp Lys Gly Asn Pro Gln Arg Ile His Tyr Phe 340 345 350 Val Ala Arg Asn Glu Leu Lys Lys Arg Leu Glu Glu Ala Lys Gln Asn 355 360 365 Ala Thr Met Thr Leu Pro Asp Ala Arg Lys His Pro Leu Trp Val Arg 370 375 380 Phe Asp Ala Arg Gly Gly Asn Leu Gln Asp Tyr Tyr Leu Thr Ala Glu 385 390 395 400 Ala Asp Asn Pro Arg Ser Arg Arg Phe Val Thr Phe Ser Gln Leu Ile 405 410 415 Trp Pro Asn Glu Ser Gly Trp Met Glu Lys Gln Asp Val Glu Val Glu 420 425 430 Leu Ala Leu Ser Lys Gln Phe Tyr Gln Gln Val Thr Leu Gln Lys Asn 435 440 445 Asp Lys Gly Lys Gln Glu Ile Glu Phe Lys Asp Lys Gly Ser Gly Ser 450 455 460 Thr Phe Ser Gly His Leu Gly Gly Ala Lys Leu Gln Leu Glu Arg Gly 465 470 475 480 Asp Leu Glu Lys Glu Glu Lys Asp Phe Glu Gly Gly Glu Ile Gly Ser 485 490 495 Val Tyr Leu Asn Ile Val Ile Asp Phe Glu Pro Leu Gln Glu Val Lys 500 505 510 Asn Gly Arg Leu Gln Ser Pro Tyr Gly Gln Val Leu Gln Leu Val Arg 515 520 525 Arg Pro Asn Glu Phe Pro Lys Val Thr Thr Tyr Lys Ser Glu Glu Leu 530 535 540 Val Glu Trp Ile Lys Ser Ser Thr Lys Asp Ser Ala Gly Val Glu Ser 545 550 555 560 Leu Glu Ser Gly Phe Arg Val Met Ser Ile Ala Leu Gly Leu Arg Thr 565 570 575 Ala Ala Ala Thr Ser Ile Phe Ser Val Glu Glu Ser Asn Asp Ala Asn 580 585 590 Ala Ala Gly Phe Ser Tyr Trp Ile Glu Gly Thr Pro Leu Val Ala Val 595 600 605 His Lys Arg Ser Tyr Met Leu Lys Leu Pro Gly Glu Gln Val Glu Lys 610 615 620 Gln Val Arg Glu Lys Arg Asp Glu Arg Gln Asp Gln Gln Arg Arg Val 625 630 635 640 Arg Phe Gln Ile Arg Ile Leu Ser Gln Val Ile Arg Met Ala Lys Lys 645 650 655 Gln Asn Arg Glu Arg Ala Asp Glu Leu Asp His Leu Ser Gln Ala Leu 660 665 670 Glu Lys Gln Lys Ser Leu Leu Asp Gln Thr Asp Arg Thr Phe Trp Asn 675 680 685 Gly Ile Val Cys Asp Leu Thr Asp Ala Leu Arg Glu Lys Glu Gly Gly 690 695 700 Trp Glu Gln Ala Val Val Gln Ile His Arg Lys Ala Glu Glu His Val 705 710 715 720 Gly Lys Val Val Gln Ala Trp Arg Lys Arg Phe Asp Ala Asp Glu Arg 725 730 735 Lys Gly Ile Ala Gly Leu Ser Met Trp Ser Ile Glu Glu Leu Asp Ser 740 745 750 Leu Arg Lys Leu Leu Ile Ser Trp Ser Arg Arg Thr Arg Asn Pro Arg 755 760 765 Glu Ile Asn Cys Phe Glu Gln Gly His Thr Ser His Gln Arg Leu Leu 770 775 780 Thr His Ile Gln Asn Val Lys Glu Asp Arg Leu Lys Gln Leu Ser His 785 790 795 800 Ala Ile Val Met Thr Ala Leu Gly Tyr Val Tyr Asp Glu Lys Lys Leu 805 810 815 Glu Trp Phe Ala Lys Tyr Pro Ala Cys Gln Val Ile Leu Phe Glu Asn 820 825 830 Leu Ser Gln Tyr Arg Ser Asn Met Asp Arg Ser Thr Lys Glu Asn Ser 835 840 845 Thr Leu Met Lys Trp Ala His Arg Ser Ile Pro Lys Tyr Val His Met 850 855 860 Gln Ala Glu Pro Tyr Gly Ile Gln Ile Gly Asp Val Arg Ala Glu Tyr 865 870 875 880 Ser Ser Arg Phe His Ala Lys Thr Gly Thr Pro Gly Ile Arg Cys Lys 885 890 895 Met Val Ser Gly His Asp Leu Gln Gly Arg Arg Phe Glu Asn Leu Gln 900 905 910 Lys Arg Leu Ile Ser Glu Gln Phe Leu Thr Glu Glu Gln Val Lys Gln 915 920 925 Leu Arg Pro Gly Asp Ile Val Pro Asp Asp Ser Gly Glu Trp Phe Met 930 935 940 Thr Leu Ser Asp Gly Ser Glu Gly Lys Glu Val Val Phe Leu Gln Ala 945 950 955 960 Asp Ile Asn Ala Ala Gln Asn Leu Gln Lys Arg Phe Trp Gln Arg Tyr 965 970 975 Asn Glu Leu Phe Lys Val Ser Cys Arg Val Leu Ile Arg Gly Glu Glu 980 985 990 Glu Tyr Leu Ile Pro Lys Thr Lys Ser Val Gln Ala Lys Leu Gly Lys 995 1000 1005 Gly Leu Phe Val Lys Lys Thr Asp Thr Val Met Lys Asp Val Tyr 1010 1015 1020 Val Trp Asp Ser Gln Ala Lys Leu Lys Gly Lys Thr Thr Phe Thr 1025 1030 1035 Glu Glu Ser Glu Ser Pro Glu Gln Leu Glu Asp Phe Gln Glu Ile 1040 1045 1050 Ile Glu Glu Ala Glu Glu Ala Lys Gly Thr Tyr Arg Thr Leu Phe 1055 1060 1065 Arg Asp Pro Ser Gly Val Phe Phe Pro Glu Phe Val Trp Ser Thr 1070 1075 1080 Gln Lys Asp Phe Trp Ser Glu Val Lys Arg Arg Leu Tyr Gly Lys 1085 1090 1095 Leu Arg Glu Arg Phe Leu Met Lys Thr Arg 1100 1105 <210> 55 <211> 1150 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="nAPG09882" <400> 55 Met Tyr Ser Ile Gly Leu Ala Leu Gly Ile Ser Ser Val Gly Trp Ser 1 5 10 15 Val Ile Asp Glu Arg Thr Gly Asn Val Ile Asp Leu Gly Ile Arg Leu 20 25 30 Phe Ser Ala Lys Asn Ser Glu Lys Asn Leu Glu Arg Arg Thr Asn Arg 35 40 45 Gly Gly Arg Arg Leu Ile Arg Arg Lys Thr Asn Arg Leu Lys Asp Ala 50 55 60 Lys Lys Ile Leu Ala Ala Val Gly Phe Tyr Glu Asp Lys Ser Leu Lys 65 70 75 80 Asn Ser Cys Pro Tyr Gln Leu Arg Val Lys Gly Leu Thr Glu Pro Leu 85 90 95 Ser Lys Gly Glu Ile Tyr Lys Val Thr Leu His Ile Leu Lys Lys Arg 100 105 110 Gly Ile Ser Tyr Leu Asp Glu Asp Asp Thr Glu Ala Ala Lys Glu Ser 115 120 125 Gln Asp Tyr Lys Glu Gln Val Arg Glu Asn Ala Gln Leu Leu Thr Lys 130 135 140 Tyr Thr Pro Gly Gln Ile Gln Leu Gln Arg Leu Lys Glu Asn Asn Arg 145 150 155 160 Val Lys Thr Gly Ile Asn Ala Gln Gly Asn Tyr Gln Leu Asn Val Phe 165 170 175 Lys Val Ser Ala Tyr Ala Asn Glu Leu Ala Thr Ile Leu Lys Thr Gln 180 185 190 Gln Ala Phe Tyr Pro Asn Glu Leu Thr Asp Asp Trp Ile Ala Leu Phe 195 200 205 Val Gln Pro Gly Ile Ala Glu Glu Ala Gly Leu Ile Tyr Arg Lys Arg 210 215 220 Pro Tyr Tyr His Gly Pro Gly Asn Glu Ala Asn Asn Ser Pro Tyr Gly 225 230 235 240 Arg Trp Ser Asp Phe Lys Lys Thr Gly Gln Pro Ala Thr Asn Ile Phe 245 250 255 Asp Lys Leu Ile Gly Lys Asp Phe Gln Gly Glu Leu Arg Ala Ser Gly 260 265 270 Leu Ser Leu Ser Ala Gln Gln Tyr Asn Leu Leu Asn Asp Leu Thr Asn 275 280 285 Leu Lys Ile Asp Gly Glu Ile Pro Leu Ser Pro Glu Gln Lys Glu Tyr 290 295 300 Ile Leu Ala Glu Leu Met Thr Lys Glu Phe Thr Arg Phe Gly Val Asn 305 310 315 320 Asp Val Val Lys Leu Leu Gly Val Lys Lys Glu Arg Leu Ser Gly Trp 325 330 335 Arg Leu Asp Lys Lys Gly Lys Pro Glu Ile His Thr Leu Lys Gly Tyr 340 345 350 Arg Asn Trp Arg Lys Ile Phe Ala Glu Ser Gly Ile Asp Leu Ala Thr 355 360 365 Leu Pro Thr Glu Thr Ile Asp Cys Leu Ala Lys Val Leu Thr Leu Asn 370 375 380 Thr Glu Arg Glu Gly Ile Glu Asn Thr Leu Ala Phe Glu Leu Ser Glu 385 390 395 400 Leu Ala Glu Ser Val Lys Leu Leu Val Leu Asp Arg Tyr Lys Glu Leu 405 410 415 Ser Gln Ser Val Ser Thr Gln Ala Trp His Arg Phe Ser Leu Lys Thr 420 425 430 Leu His Leu Leu Ile Pro Glu Leu Met Asn Ala Thr Ser Glu Gln Asn 435 440 445 Thr Leu Leu Glu Gln Phe Gln Leu Lys Ser Asp Val Arg Lys Arg Tyr 450 455 460 Ser Glu Tyr Lys Lys Leu Pro Thr Lys Asp Val Leu Thr Glu Ile Tyr 465 470 475 480 Asn Pro Thr Val Asn Lys Thr Val Ser Gln Ala Phe Lys Val Ile Asp 485 490 495 Ala Leu Leu Val Lys Tyr Gly Lys Glu Gln Ile Arg Tyr Ile Thr Ile 500 505 510 Glu Met Pro Arg Asp Asp Asn Glu Glu Asp Glu Lys Lys Arg Ile Lys 515 520 525 Glu Leu His Ala Lys Asn Ser Gln Arg Lys Asn Asp Ser Gln Ser Tyr 530 535 540 Phe Met Gln Lys Ser Gly Trp Ser Gln Glu Lys Phe Gln Thr Thr Ile 545 550 555 560 Gln Lys Asn Arg Arg Phe Leu Ala Lys Leu Leu Tyr Tyr Tyr Glu Gln 565 570 575 Asp Gly Ile Cys Ala Tyr Thr Gly Leu Ser Ile Ser Pro Glu Leu Leu 580 585 590 Val Ser Asp Ser Thr Glu Ile Asp His Ile Ile Pro Ile Ser Ile Ser 595 600 605 Leu Asp Asp Ser Ile Asn Asn Lys Val Leu Val Leu Ser Lys Ala Asn 610 615 620 Gln Val Lys Gly Gln Gln Thr Pro Tyr Asp Ala Trp Met Asp Gly Ser 625 630 635 640 Phe Lys Lys Ile Asn Gly Lys Phe Ser Asn Trp Asp Asp Tyr Gln Lys 645 650 655 Trp Val Glu Ser Cys His Phe Ser His Lys Lys Glu Asn Asn Leu Leu 660 665 670 Glu Thr Arg Asn Ile Phe Asp Ser Glu Gln Val Glu Lys Phe Leu Ala 675 680 685 Arg Asn Leu Asn Asp Thr Arg Tyr Ala Ser Arg Leu Val Leu Asn Thr 690 695 700 Leu Gln Ser Phe Phe Ala Asn Gln Glu Thr Lys Val Arg Val Val Asn 705 710 715 720 Gly Ser Phe Thr His Thr Leu Arg Lys Lys Trp Gly Ala Asp Leu Asp 725 730 735 Lys Thr Arg Glu Thr His His His His Ala Val Asp Ala Thr Leu Cys 740 745 750 Ala Val Thr Pro Phe Val Lys Val Ser Arg Tyr His Tyr Ala Val Lys 755 760 765 Glu Glu Thr Gly Glu Lys Val Met Arg Glu Ile Asp Phe Glu Thr Gly 770 775 780 Glu Ile Val Asp Glu Met Ser Tyr Arg Glu Phe Lys Lys Ser Lys Lys 785 790 795 800 Tyr Glu Arg Lys Thr Tyr Gln Val Lys Trp Pro Asn Phe Arg Glu Gln 805 810 815 Leu Lys Pro Val Asn Leu His Pro Arg Ile Lys Phe Ser His Gln Val 820 825 830 Asp Arg Lys Ala Asn Arg Lys Leu Ser Asp Ala Thr Ile Tyr Ser Val 835 840 845 Arg Glu Lys Thr Glu Val Lys Thr Leu Lys Ser Gly Lys Gln Lys Ile 850 855 860 Thr Thr Asp Glu Tyr Thr Ile Gly Lys Ile Lys Asp Ile Tyr Thr Val 865 870 875 880 Asp Gly Trp Glu Ala Phe Lys Lys Lys Gln Asp Lys Leu Leu Met Lys 885 890 895 Asp Leu Asp Glu Lys Thr Tyr Glu Arg Leu Leu Ser Ile Ala Glu Thr 900 905 910 Thr Pro Asp Phe Gln Glu Val Glu Glu Lys Asn Gly Lys Val Lys Arg 915 920 925 Val Lys Arg Ser Pro Phe Ala Val Tyr Cys Glu Glu Asn Asp Ile Pro 930 935 940 Ala Ile Arg Lys Tyr Ala Lys Lys Asn Asn Gly Pro Leu Ile Arg Ser 945 950 955 960 Leu Lys Tyr Tyr Asp Gly Lys Leu Asn Lys His Ile Asn Ile Thr Lys 965 970 975 Asp Ser Gln Gly Arg Pro Val Glu Lys Thr Lys Asn Gly Arg Lys Val 980 985 990 Thr Leu Gln Ser Leu Lys Pro Tyr Arg Tyr Asp Ile Tyr Gln Asp Leu 995 1000 1005 Glu Thr Lys Ala Tyr Tyr Thr Val Gln Leu Tyr Tyr Ser Asp Leu 1010 1015 1020 Arg Phe Val Glu Gly Lys Tyr Gly Ile Thr Glu Lys Glu Tyr Met 1025 1030 1035 Lys Lys Val Ala Glu Gln Thr Lys Gly Gln Val Val Arg Phe Cys 1040 1045 1050 Phe Ser Leu Gln Lys Asn Asp Gly Leu Glu Ile Glu Trp Lys Asp 1055 1060 1065 Ser Gln Cys Tyr Asp Val Arg Phe Tyr Asn Phe Gln Ser Ala Asn 1070 1075 1080 Ser Ile Asn Phe Lys Gly Leu Glu Gln Glu Met Met Pro Ala Glu 1085 1090 1095 Asn Gln Phe Lys Gln Lys Pro Tyr Asn Asn Gly Ala Ile Asn Leu 1100 1105 1110 Asn Ile Ala Lys Tyr Gly Lys Glu Gly Lys Lys Leu Arg Lys Phe 1115 1120 1125 Asn Thr Asp Ile Leu Gly Lys Lys His Tyr Leu Tyr Tyr Glu Lys 1130 1135 1140 Glu Pro Lys Asn Ile Ile Lys 1145 1150 <210> 56 <211> 1068 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="nAPG03850" <400> 56 Met Lys Tyr Val Leu Gly Leu Ala Ile Gly Ile Ala Ser Cys Gly Trp 1 5 10 15 Ala Val Ile Asn Gln Glu Lys His Arg Ile Glu Asp Leu Gly Val Arg 20 25 30 Ile Phe Asp Lys Ala Glu Asn Pro Lys Asp Gly Lys Ser Leu Ala Thr 35 40 45 Pro Arg Arg Asp Ala Arg Ser Thr Arg Arg Thr Leu Arg Arg Lys Lys 50 55 60 His Arg Met Gln Arg Ile Lys Ile Leu Leu Val Lys His Gly Leu Leu 65 70 75 80 Ser Lys Thr Glu Ile Asp His Leu Tyr Glu Ser Ala Thr Glu Ile Asp 85 90 95 Val Trp Tyr Leu Arg Leu Asn Ala Leu Glu Arg Arg Leu Asn Pro Lys 100 105 110 Glu Phe Ala Arg Val Leu Ile His Leu Ala Lys Arg Arg Gly Phe Lys 115 120 125 Ser Asn Arg Lys Glu Thr Thr Leu Ser Glu Asn Gly Gln Ile Leu Glu 130 135 140 Asn Ile Ser Glu Asn Leu Gln Ile Met Glu Gln Gln Asn Tyr Arg Thr 145 150 155 160 Val Gly Glu Met Ile Leu Lys Asp Lys Lys Phe Glu Asn His Lys Arg 165 170 175 Asn Lys Asp Gly Thr Tyr Ile Gly Thr Val Thr Arg Gln Gln Leu Lys 180 185 190 Glu Glu Ile Gln Met Ile Phe Asn Ala Gln Arg Leu Tyr Lys Asn Asp 195 200 205 Tyr Ala Thr Glu Glu Phe Glu Ser Ser Tyr Leu Glu Ile Trp Ala Ser 210 215 220 Gln Arg Pro Tyr Ala Ser Lys Asp Gln Ile Glu Lys Met Ile Gly Tyr 225 230 235 240 Cys Thr Leu Glu Pro Lys Glu Lys Arg Val Pro Lys Ala Ser Trp Ser 245 250 255 Phe Gln Tyr Phe Val Ala Leu Gln Thr Ile Asn Asn Leu Arg Leu Ile 260 265 270 Asn Lys Asp Arg Ile Glu Glu Leu Ser Phe Glu Glu Lys Asn Gln Ile 275 280 285 Met Asn Leu Ala Leu Glu Lys Ser Ile Val Lys Tyr Ile Asp Ile Arg 290 295 300 Lys Leu Leu Ser Ile Pro Asn Glu Phe His Phe Asn Asn Leu Leu Tyr 305 310 315 320 Ser Ala Asp Thr Val Asp Thr Ala Val Glu Asn Lys Lys Cys Ile Glu 325 330 335 Phe Lys Glu Tyr His Ser Ile Asn Lys Leu Tyr Lys Gln Ile Tyr Gly 340 345 350 Lys Ser Val Pro Asn Leu Leu Pro Ile Asp Tyr Asp Thr Ile Ala Cys 355 360 365 Gly Leu Thr Ile Phe Lys Asp Asp Lys Asp Ile Leu Ala Tyr Leu Gln 370 375 380 Asn Lys Tyr Val Asn Ala Lys Gly Lys Pro Ile Ser Asn Leu Ala Lys 385 390 395 400 Lys Thr Tyr Asp Asp Thr Phe Ile Gln Ala Leu Leu Thr Leu Asn Phe 405 410 415 Ser Lys Met Gly His Leu Ser Phe Lys Ala Leu Lys Asn Ile Ile Pro 420 425 430 Phe Leu Glu Glu Gly Leu Ser Tyr Asp Lys Ala Cys Glu Lys Ala Gly 435 440 445 Tyr Asn Phe Lys Gly Thr Ser His Ala Glu Lys Thr Lys Tyr Leu Pro 450 455 460 Val Ile Pro Gln Asn Thr Asn Pro Val Val His Arg Ala Leu Ser Gln 465 470 475 480 Thr Arg Lys Val Ile Asn Ala Ile Ile Lys Lys Tyr Gly Ser Pro Ser 485 490 495 Ala Ile His Ile Glu Thr Ala Arg Glu Leu Ser Lys Thr Phe Gln Glu 500 505 510 Arg Lys Glu Ile Asp Ser Met Tyr Gln Asp Asn Ser Lys Lys Asn Glu 515 520 525 His Ala Ile His Lys Leu Lys Glu Leu Gly Leu Ile Asn Pro Ser Gly 530 535 540 Ile Asn Ile Val Lys Phe Lys Leu Trp Asn Glu Gln Asp Gly Arg Cys 545 550 555 560 Met Tyr Ser Gly Lys Tyr Ile Glu Pro His Arg Leu Phe Glu Glu Glu Gly 565 570 575 Tyr Thr Glu Val Asp His Ile Leu Pro Tyr Ser Arg Ser Leu Asp Asp 580 585 590 Ser Tyr Asn Asn Lys Ala Leu Thr Leu Gly Ile Glu Asn Gln Arg Lys 595 600 605 Gly Asn Lys Thr Pro Tyr Glu Tyr Ile Gly Lys Thr Ser Ile Trp His 610 615 620 Glu Phe Glu Thr Arg Val Gln Ser Asn Lys Arg Ile Asn Lys Lys Lys 625 630 635 640 Gln Gln Lys Leu Leu Leu Gln Tyr Phe Ser Tyr Thr Arg Glu Gln Glu 645 650 655 Phe Ile Lys Arg Asn Leu Asn Asp Thr Arg Tyr Ala Thr Ile Tyr Leu 660 665 670 Ser Thr Leu Ile Gln Gln His Leu Ile Phe Ser Glu Ser Ser Arg Lys 675 680 685 Lys Lys Val His Thr Val Ser Gly Ile Ile Thr Ser His Leu Arg Ser 690 695 700 Arg Trp Gly Phe Asn Lys Asp Arg Lys Glu Gly His Ile His His Ala 705 710 715 720 Leu Asp Ala Val Ile Val Ala Val Thr Ser Asp His Met Ile Gln Arg 725 730 735 Val Thr Lys Tyr Tyr Lys Leu Lys Glu Leu Asn Arg Asn Leu Gln Ala 740 745 750 Lys Arg Met Gln Phe Pro Glu Pro Trp Glu Gly Phe Arg Leu Glu Leu 755 760 765 Glu Ala Arg Ile Ser Pro Asn Thr Gln Gln Tyr Leu Lys Arg Ile Leu 770 775 780 Phe Lys Asn Tyr Ala Asp Val Asn Leu Ser Glu Ile Lys Pro Ile Phe 785 790 795 800 Val Ser Arg Met Pro Lys Arg Ser Ile Thr Gly Glu Leu His Gln Glu 805 810 815 Thr Ile Arg Lys Leu Ile Gly Tyr Asn Glu Lys Gly Lys Val Leu Thr 820 825 830 Ala Ile Lys Thr Lys Leu Glu Asp Ile Pro Phe Asp Ala Asn Gly Asp 835 840 845 Phe Pro Met Tyr Gly Lys Glu Thr Asp Leu Tyr Thr Tyr Asn Ala Ile 850 855 860 Lys Glu Arg Tyr Leu Ser His Lys Lys Asp Lys Arg Lys Ser Phe Gln 865 870 875 880 Asp Pro Leu Tyr Lys Pro Thr Lys Ser Gly Glu Ile Gly Pro Leu Ile 885 890 895 Lys Ser Ile Lys Ile Met Asp Thr Arg Thr Ile Val Asn Pro Val Asn 900 905 910 Gln Gly Lys Gly Val Val Tyr Asn Ser Lys Ile Ala Arg Thr Asp Val 915 920 925 Phe Lys Lys Asp Glu Lys Tyr Tyr Leu Ile Pro Ile Tyr Thr Ile Asp 930 935 940 Leu Leu Lys Asn Ile Leu Pro Gln Lys Ala Ile Thr Ala Gly Lys Gly 945 950 955 960 Tyr Glu Asp Trp Thr Thr Ile Asp Pro Ser Phe Thr Phe Leu Phe Ser 965 970 975 Leu Phe Pro Asn Asp Leu Ile Gln Ile Val Pro Ser Lys Asn Lys Thr 980 985 990 Ile Lys Ala Arg Thr Thr Val Ser Lys Lys Glu Val Leu Leu Pro Ser 995 1000 1005 Leu Thr Gly Tyr Phe Lys Gly Val His Ser Gly Thr Ala Gly Ile 1010 1015 1020 Thr Val Glu Thr His Asp Gly Ser Val Ile Ala Asn Val Gly Ser 1025 1030 1035 Lys Gln Leu Leu Leu Phe Glu Lys Tyr Gln Val Asp Val Leu Gly 1040 1045 1050 His Tyr Thr Lys Ile Lys Glu Glu Lys Arg Ile Gly Met Val Ile 1055 1060 1065 <210> 57 <211> 1081 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="nAPG07553" <400> 57 Met Gln Tyr Val Leu Gly Leu Ala Ile Gly Ile Ala Ser Cys Gly Trp 1 5 10 15 Ala Val Ile Asn Gln Glu Lys Glu Arg Ile Glu Asp Leu Gly Val Arg 20 25 30 Ile Phe Asp Lys Ala Glu Asn Pro Lys Asp Gly Lys Ser Leu Ala Ala 35 40 45 Pro Arg Arg Asp Ala Arg Ser Thr Arg Arg Thr Leu Arg Arg Lys Lys 50 55 60 His Arg Met Gln Arg Ile Lys Ile Leu Leu Val Lys His Gly Leu Leu 65 70 75 80 Ser Gln Thr Glu Leu Asp His Leu Tyr Glu Ser Ala Thr Glu Val Asp 85 90 95 Val Trp Asn Leu Arg Leu Asp Ala Ile Glu Arg Lys Leu Asn Pro Lys 100 105 110 Glu Phe Thr Arg Val Leu Ile His Leu Ala Lys Arg Arg Gly Phe Lys 115 120 125 Ser Asn Ser Lys Glu Thr Thr Leu Ser Glu Asn Gly Gln Ile Leu Glu 130 135 140 Ser Ile Ser Glu Asn Gln Gln Ile Met Glu Gln Lys Asn Tyr Lys Thr 145 150 155 160 Ile Gly Glu Met Ile Leu Lys Asp Lys Lys Phe Glu Asn His Lys Arg 165 170 175 Asn Lys Asp Gly Thr Tyr Ile Gly Thr Val Thr Arg Gln Gln Leu Gln 180 185 190 Asp Glu Ile Gln Ile Ile Phe Asn Ala Gln Arg Leu Tyr Lys Asn Asn 195 200 205 Tyr Ala Thr Lys Glu Phe Glu Ser Ser Tyr Leu Glu Ile Trp Ala Ser 210 215 220 Gln Arg Pro Tyr Ala Ser Lys Asp Gln Ile Glu Lys Met Ile Gly Tyr 225 230 235 240 Cys Thr Leu Glu Gln Lys Glu Lys Arg Val Pro Arg Ala Ser Trp Ser 245 250 255 Phe Gln Tyr Phe Val Ala Leu His Thr Ile Asn Asn Leu Arg Leu Ile 260 265 270 Ser Lys Asp Arg Ile Glu Glu Leu Ser Phe Lys Glu Lys Lys Gln Ile 275 280 285 Met Asn Leu Ala Leu Glu Lys Pro Ile Val Lys Tyr Ile Asp Ile Arg 290 295 300 Lys Leu Leu Ser Ile Pro Asn Glu Leu His Phe Asn Ser Leu Leu Tyr 305 310 315 320 Ser Ala Asp Thr Val Asp Thr Thr Val Glu Asn Arg Lys Cys Ile Glu 325 330 335 Leu Lys Glu Tyr His Ser Ile Asn Lys Val Tyr Lys Gln Ile Tyr Gly 340 345 350 Lys Asn Ala Leu Asn Leu Leu Pro Ile Asp Tyr Asp Thr Ile Ala Tyr 355 360 365 Gly Leu Thr Ile Phe Lys Asp Asp Lys Asp Ile Leu Glu His Leu Lys 370 375 380 Asn Lys Tyr Val Asn Ala Lys Gly Lys Pro Ile Asn Asn Leu Ala Lys 385 390 395 400 Lys Thr Tyr Asp Asp Thr Phe Ile Gln Ala Leu Leu Thr Leu Asn Phe 405 410 415 Ser Lys Met Gly His Leu Ser Phe Lys Ala Leu Lys Asn Ile Ile Pro 420 425 430 Phe Leu Glu Glu Gly Leu Ser Tyr Asp Lys Ala Cys Glu Lys Ala Gly 435 440 445 Tyr Asn Phe Lys Gly Thr Ser Tyr Thr Glu Gln Thr Lys Tyr Leu Pro 450 455 460 Val Ile Pro Gln Asn Thr Asn Pro Val Val His Arg Ala Leu Ser Gln 465 470 475 480 Thr Lys Lys Val Ile Asn Ala Ile Ile Lys Lys Tyr Gly Ser Pro Asn 485 490 495 Ala Ile His Ile Glu Thr Ala Arg Glu Leu Ser Lys Thr Phe Gln Glu 500 505 510 Arg Lys Glu Ile Asp Ser Met Tyr Gln Asp Asn Ser Lys Lys Asn Glu 515 520 525 His Ala Ile His Lys Leu Lys Glu Leu Gly Asn Ile Asn Pro Ser Gly 530 535 540 Ile Asn Ile Val Lys Phe Lys Leu Trp Asn Glu Gln Asp Gly Lys Cys 545 550 555 560 Met Tyr Ser Gly Lys Tyr Ile Glu Pro His Arg Leu Phe Glu Glu Glu Gly 565 570 575 Tyr Thr Glu Val Asp His Ile Leu Pro Tyr Ser Arg Ser Leu Asp Asp 580 585 590 Ser Tyr Asn Asn Lys Thr Leu Thr Leu Gly Ile Glu Asn Gln Arg Lys 595 600 605 Gly Asn Lys Thr Pro Tyr Glu Tyr Met Gly Asn Thr Ser Ile Trp Asp 610 615 620 Glu Tyr Glu Ile Arg Val Gln Ser Asn Lys Lys Ile Asn Lys Lys Lys 625 630 635 640 Gln Gln Lys Leu Leu Leu Gln His Phe Ser Tyr Ala Arg Glu Gln Glu 645 650 655 Phe Ile Glu Arg Asn Leu Asn Asp Thr Arg Tyr Ala Thr Ile Tyr Leu 660 665 670 Ser Ser Leu Ile Gln Gln His Leu Ile Phe Ser Glu Ser Ser Ser Arg Lys 675 680 685 Lys Lys Val His Thr Val Ser Gly Ile Ile Thr Ser His Leu Arg Ser 690 695 700 Arg Trp Gly Phe Asn Lys Asp Arg Lys Glu Gly His Ile His His Ala 705 710 715 720 Leu Asp Ala Val Ile Val Ala Val Thr Ser Asp His Met Ile Gln Arg 725 730 735 Val Thr Lys Tyr Tyr Lys Leu Lys Glu Leu Asn Arg Asn Leu Gln Ala 740 745 750 Lys Arg Met Pro Phe Pro Glu Pro Trp Glu Gly Phe Arg Leu Glu Leu 755 760 765 Glu Ala Arg Ile Ser Pro Asn Thr Gln Gln Tyr Leu Lys Gly Leu Arg 770 775 780 Phe Lys Asn Tyr Ala Asp Val Asn Leu Cys Glu Ile Lys Pro Ile Phe 785 790 795 800 Val Ser Lys Met Pro Lys Arg Ser Ile Thr Gly Glu Leu His Gln Glu 805 810 815 Thr Ile Arg Lys Phe Ile Gly Tyr Asn Glu Lys Gly Lys Val Leu Thr 820 825 830 Ala Ile Lys Thr Lys Leu Glu Asp Ile Pro Phe Asp Ala Asn Gly Asp 835 840 845 Phe Pro Met Tyr Gly Lys Glu Thr Asp Leu Tyr Thr Tyr Asn Ser Ile 850 855 860 Lys Glu Arg Tyr Leu Ser His Lys Lys Asp Lys Arg Lys Ser Phe Gln 865 870 875 880 Glu Pro Leu Tyr Lys Pro Thr Lys Ser Gly Gly Ile Gly Pro Leu Ile 885 890 895 Lys Ser Ile Lys Ile Met Asp Thr Arg Thr Ile Val Asn Pro Val Asn 900 905 910 Gln Gly Lys Gly Val Val Tyr Asn Ser Lys Ile Ala Arg Thr Asp Val 915 920 925 Phe Lys Lys Asp Asp Lys Tyr Tyr Leu Ile Pro Ile Tyr Thr Ile Asp 930 935 940 Leu Met Lys Asn Ile Leu Pro Gln Lys Ala Ile Thr Ala Gly Lys Gly 945 950 955 960 Tyr Glu Asp Trp Ile Thr Ile Asp His Ser Phe Thr Phe Leu Phe Ser 965 970 975 Leu Phe Pro Asn Asp Leu Ile Lys Ile Val Pro Ser Lys Asn Lys Glu 980 985 990 Ile Lys Ala Arg Ser Thr Ser Ser Lys Lys Glu Ile Leu Leu Pro Ser 995 1000 1005 Leu Ile Gly Tyr Phe Lys Ser Val His Ser Gly Thr Ala Gly Ile 1010 1015 1020 Thr Val Glu Ser His Asp Gly Arg Phe Ile Ala Asn Val Gly Ser 1025 1030 1035 Lys Gln Leu Leu Leu Phe Glu Lys Tyr Gln Val Asp Val Leu Gly 1040 1045 1050 His Tyr Thr Lys Ile Lys Glu Glu Lys Arg Ile Gly Met Ala Thr 1055 1060 1065 Cys Asn Asp Asn Lys Lys Ser Thr Ala Phe Gly Ser Leu 1070 1075 1080 <210> 58 <211> 1150 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="nAPG05586" <400> 58 Met Tyr Ser Ile Gly Leu Ala Leu Gly Ile Ser Ser Val Gly Trp Ser 1 5 10 15 Val Ile Asp Glu Glu Thr Gly Lys Ile Val Asp Leu Gly Val Arg Leu 20 25 30 Phe Ser Ala Lys Asn Ser Glu Lys Asn Leu Glu Arg Arg Thr Ser Arg 35 40 45 Gly Ala Arg Arg Leu Ile Arg Arg Lys Thr Asn Arg Leu Lys Asp Ala 50 55 60 Lys Lys Leu Leu Glu Ala Ile Gly Phe Tyr Glu Asp Lys Ala Leu Lys 65 70 75 80 Asn Val Cys Pro Tyr Gln Leu Arg Val Lys Gly Leu Thr Glu Gly Leu 85 90 95 Thr Lys Gly Glu Leu Tyr Lys Val Val Leu His Ile Val Lys Lys Arg 100 105 110 Gly Ile Ser Tyr Leu Asp Glu Asp Asp Ala Glu Ala Ala Lys Glu Ser 115 120 125 Gln Asp Tyr Lys Glu Gln Val Arg Lys Asn Ala Gln Leu Leu Thr Lys 130 135 140 Tyr Thr Pro Gly Gln Ile Gln Leu Gln Arg Leu Lys Glu Asn Asn Arg 145 150 155 160 Val Lys Thr Gly Ile Asn Gly Gln Gly His Tyr Gln Leu Asn Val Phe 165 170 175 Lys Val Ser Ala Tyr Ala Asp Glu Leu Ala Thr Ile Leu Lys Thr Gln 180 185 190 Gln Ala Leu Tyr Pro Asn Glu Leu Thr Asp Asp Trp Ile Ala Leu Phe 195 200 205 Val Gln Pro Gly Ile Ala Glu Asn Ala Gly Leu Ile Tyr Arg Lys Arg 210 215 220 Pro Tyr Tyr His Gly Pro Gly Asn Glu Ala Asn Asn Ser Pro Tyr Gly 225 230 235 240 Arg Trp Ser Asp Phe Gln Lys Thr Gly Gln Pro Ala Ala Asn Ile Phe 245 250 255 Asp Lys Leu Ile Gly Lys Asp Phe Gln Gly Glu Leu Arg Ala Ser Gly 260 265 270 Leu Ser Leu Ser Ala Gln Gln Tyr Asn Leu Leu Asn Asp Leu Thr Asn 275 280 285 Leu Lys Ile Asp Gly Glu Val Ser Leu Ser Pro Glu Gln Lys Glu Phe 290 295 300 Ile Leu Thr Glu Leu Met Thr Lys Glu Phe Ala Arg Phe Gly Val Asn 305 310 315 320 Asp Ile Ala Lys Leu Leu Gly Val Lys Lys Glu Gln Leu Ser Gly Trp 325 330 335 Arg Leu Asp Lys Lys Gly Lys Pro Glu Ile His Thr Leu Lys Gly Tyr 340 345 350 Arg Asn Trp Arg Lys Ile Phe Ala Glu Ala Gly Ile Asp Leu Ala Thr 355 360 365 Leu Pro Thr Glu Thr Ile Asp Cys Leu Ala Lys Val Leu Thr Leu Asn 370 375 380 Thr Glu Arg Glu Gly Val Glu Asn Thr Leu Ala Phe Glu Leu Pro Glu 385 390 395 400 Leu Ala Glu Pro Val Lys Ser Leu Val Leu Asp His Tyr Lys Glu Leu 405 410 415 Ser Gln Ser Ile Ser Thr Gln Ala Trp His Arg Phe Ser Leu Lys Thr 420 425 430 Leu His Leu Leu Ile Pro Glu Leu Ile Lys Ser Thr Ser Glu Gln Asn 435 440 445 Thr Leu Leu Glu Gln Phe Gln Leu Lys Ala Gly Val Arg Lys Arg Tyr 450 455 460 Ser Asp Tyr Lys Lys Leu Pro Thr Lys Glu Val Leu Ala Glu Ile Tyr 465 470 475 480 Asn Pro Thr Val Asn Lys Thr Val Ser Gln Ala Phe Lys Val Met Asp 485 490 495 Ala Leu Leu Glu Lys Tyr Gly Lys Asp Gln Ile His Tyr Ile Thr Val 500 505 510 Glu Met Pro Arg Asp Asp Asn Glu Glu Glu Glu Glu Arg Lys Arg Ile Lys 515 520 525 Glu Leu Gln Thr Lys Asn Ser Gln Arg Lys Asn Asp Ser Gln Gln Tyr 530 535 540 Phe Leu Gln Lys Ser Gly Trp Ser Gln Glu Lys Phe Gln Ala Thr Ile 545 550 555 560 His Lys Asn Arg Arg Phe Leu Ala Lys Leu Leu Tyr Tyr Phe Glu Gln 565 570 575 Asp Gly Val Cys Ala Tyr Thr Gly Asn Pro Ile Ser Pro Glu Leu Leu 580 585 590 Val Ser Asp Ser Thr Glu Ile Asp His Ile Ile Pro Ile Ser Ile Ser 595 600 605 Leu Asp Asp Ser Ile Asn Asn Lys Val Leu Val Leu Ser His Ala Asn 610 615 620 Gln Val Lys Gly Gln Gln Thr Pro Tyr Asp Ala Arg Met Ala Gly Ala 625 630 635 640 Phe Asn Lys Ile Asn Gly Lys Phe Ser Asn Trp Asp Glu Tyr Gln Lys 645 650 655 Trp Val Glu Ser Arg Pro Phe Ser Arg Lys Lys Val Asn Asn Leu Leu 660 665 670 Glu Thr Arg Asn Ile Phe Asp Ser Glu Gln Val Gln Lys Phe Leu Ser 675 680 685 Arg Asn Leu Asn Asp Thr Arg Tyr Ala Ser Arg Leu Val Leu Asn Thr 690 695 700 Leu Gln Ser Phe Phe Glu Asn Gln Asp Thr Ile Val Arg Val Val Asn 705 710 715 720 Gly Ser Phe Thr His Thr Leu Arg Lys Lys Trp Gly Ala Asp Leu Asp 725 730 735 Lys Thr Arg Glu Thr His His His His Ala Val Asp Ala Thr Leu Cys 740 745 750 Ala Val Thr Pro Phe Val Lys Val Ser Arg Tyr His Tyr Ala Val Asn 755 760 765 Glu Glu Thr Gly Glu Lys Phe Met Arg Glu Ile Asp Val Glu Thr Gly 770 775 780 Glu Ile Leu Asp Glu Ile Pro Tyr Arg Glu Tyr Lys Lys Ala Lys His 785 790 795 800 Tyr Glu Arg Lys Thr Tyr Gln Val Lys Trp Ser Asn Phe Arg Glu Gln 805 810 815 Leu Lys Pro Ile Thr Ile His Pro Lys Ile Lys Phe Ser His Gln Val 820 825 830 Asp Arg Lys Ala Asn Arg Lys Leu Ser Asp Ala Thr Ile Tyr Ser Val 835 840 845 Arg Glu Lys Thr Glu Val Lys Thr Leu Lys Ser Gly Lys Glu Lys Ile 850 855 860 Thr Thr Asp Glu Tyr Thr Ile Gly Lys Ile Lys Asp Ile Tyr Thr Val 865 870 875 880 Asp Gly Trp Glu Ala Phe Lys Lys Lys Gln Asp Lys Leu Leu Met Lys 885 890 895 Glu Phe Asp Glu Lys Thr Tyr Glu Leu Leu Val Thr Ile Ala Ala Thr 900 905 910 Thr Pro Asp Phe Gln Glu Val Glu Glu Lys Asn Gly Lys Val Lys Arg 915 920 925 Val Lys Arg Ser Pro Phe Ala Val Tyr Cys Glu Glu Asn Gly Ile Pro 930 935 940 Ala Ile Arg Lys Tyr Ala Lys Lys Asn Asn Gly Pro Val Ile Arg Ser 945 950 955 960 Leu Lys Tyr Tyr Asp Gly Lys Leu Asn Lys His Ile Asn Ile Thr Lys 965 970 975 Asp Glu Lys Gly Arg Pro Val Glu Gln Thr Lys Asn Gly Arg Lys Val 980 985 990 Thr Leu Gln Ser Leu Lys Pro Tyr Arg Tyr Asp Ile Tyr Gln Asp Leu 995 1000 1005 Glu Thr Lys Ala Tyr Tyr Thr Val Gln Leu Tyr Tyr Ser Asp Leu 1010 1015 1020 Arg Phe Val Glu Gly Glu Tyr Gly Ile Thr Glu Lys Glu Tyr Met 1025 1030 1035 Lys Lys Val Ala Glu Gln Thr Lys Gly Gln Val Val Arg Phe Cys 1040 1045 1050 Phe Ser Leu Gln Lys Asn Asp Gly Leu Glu Ile Glu Trp Lys Asp 1055 1060 1065 Ser Gln Arg Tyr Asp Val Arg Phe Tyr Asn Phe Gln Ser Ala Asn 1070 1075 1080 Ser Ile Asn Phe Lys Gly Leu Glu Gln Glu Met Ile Pro Ala Glu 1085 1090 1095 Asn Gln Phe Lys Gln Lys Pro Tyr Asn Asn Gly Ala Ile Asn Leu 1100 1105 1110 Asn Ile Ala Lys Tyr Gly Lys Glu Gly Lys Lys Leu Arg Lys Phe 1115 1120 1125 Asn Thr Asp Ile Leu Gly Lys Lys His His Leu Ser Tyr Glu Lys 1130 1135 1140 Glu Pro Lys Asn Ile Ile Lys 1145 1150 <210> 59 <211> 1052 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="nAPG01604" <400> 59 Met Val Thr Lys Tyr Ile Leu Gly Leu Ala Ile Gly Ile Thr Ser Val 1 5 10 15 Gly Tyr Gly Ile Ile Asn Tyr Glu Asp Lys Thr Ile Ile Asp Ala Gly 20 25 30 Val Arg Leu Phe Pro Glu Ala Asn Val Glu Asn Asn Glu Gly Arg Arg 35 40 45 Ser Lys Arg Gly Ala Arg Arg Leu Lys Arg Arg Arg Ile His Arg Leu 50 55 60 Asp Arg Ile Lys Gln Leu Leu Ser Glu Tyr Asn Leu Val Asp Leu Asp 65 70 75 80 Asn Ile Pro Gln Ser Pro Ser Pro Tyr Glu Ile Arg Val Lys Gly Leu 85 90 95 Arg Glu Glu Leu Ser Lys Asp Glu Leu Val Ile Ala Leu Leu His Ile 100 105 110 Ala Lys Arg Arg Gly Ile His Asn Val Glu Ala Val Asp Glu Thr Gln 115 120 125 Asp Glu Gly Asn Glu Leu Ser Thr Lys Glu Gln Leu Ala Lys Asn Asn 130 135 140 Asn Leu Leu Lys Asp Lys Tyr Val Cys Glu Leu Leu Leu Glu Arg Leu 145 150 155 160 Lys Asp Gly Lys Val Arg Gly Glu Lys Asn Arg Phe Lys Thr Thr Asp 165 170 175 Ile Ile Lys Glu Val Lys Gln Leu Leu Glu Thr Gln Lys Glu Ala His 180 185 190 Gln Leu Asp Asp Asp Phe Ile Asn Arg Tyr Ile Asp Leu Ile Glu Thr 195 200 205 Arg Arg Glu Tyr Phe Glu Gly Pro Gly Lys Gly Ser Pro Phe Gly Trp 210 215 220 Gly Gly Asp Leu Lys Lys Trp Tyr Glu Thr Leu Met Gly His Cys Thr 225 230 235 240 Tyr Phe Pro Asn Glu Leu Arg Ser Val Lys Tyr Ser Tyr Ser Ala Asp 245 250 255 Leu Phe Asn Ala Leu Asn Asp Leu Asn Asn Leu Val Ile Gln Arg Glu 260 265 270 Gly Asn Ser Lys Leu Glu Tyr His Glu Lys Tyr His Ile Ile Glu Asn 275 280 285 Val Phe Lys Gln Lys Lys Lys Pro Thr Leu Lys Gln Ile Ala Asn Glu 290 295 300 Ile Gly Val Ser Pro Asp Asp Ile Lys Gly Phe Arg Ile Asn Lys Ser 305 310 315 320 Gly Lys Glu Thr Phe Thr Glu Phe Lys Leu Tyr His Asp Leu Lys Lys 325 330 335 Val Leu Ile Asp Gln Ser Ile Leu Glu Asn Val Gln Leu Leu Asp Gln 340 345 350 Ile Ala Glu Ile Leu Thr Ile Tyr Gln Asp Lys Glu Ser Ile Ile Asn 355 360 365 Glu Leu Asn Gln Leu Ser Glu Ile Ile Asn Glu Gln Asp Lys Glu Ser 370 375 380 Ile Ser Asn Leu Ser Gly Tyr Asn Gly Thr His Arg Leu Ser Leu Lys 385 390 395 400 Cys Ile Asn Leu Val Ile Glu Glu Leu Trp His Thr Ser Arg Asn Gln 405 410 415 Met Glu Ile Phe Thr Tyr Leu Asn Ile Lys Pro Lys Lys Ile Asp Leu 420 425 430 Ala Lys Thr Asn Lys Ile Pro Lys Asn Met Ile Asp Glu Phe Ile Leu 435 440 445 Ser Pro Val Val Lys Arg Thr Phe Gly Gln Ala Ile Asn Val Ile Asn 450 455 460 Lys Val Ile Glu Lys Tyr Gly Val Pro Glu Asp Ile Ile Ile Glu Leu 465 470 475 480 Ala Arg Glu Ser Asn Ser Lys Asp Lys Gln Lys Phe Ile Asn Ser Leu 485 490 495 Gln Lys Lys Asn Glu Thr Thr Arg Lys Arg Ile Asn Glu Ile Ile Gly 500 505 510 Gln Tyr Gly Asn Gln Asn Ala Lys Arg Leu Val Glu Lys Ile Arg Leu 515 520 525 His Asp Glu Gln Glu Gly Lys Cys Leu Tyr Ser Leu Glu Ser Ile Pro 530 535 540 Leu Glu Asp Leu Ile Asn Asn Pro Gln Tyr Tyr Glu Val Asp His Ile 545 550 555 560 Ile Pro Arg Ser Val Ser Phe Asp Asn Ser Tyr Gln Asn Lys Val Leu 565 570 575 Val Lys Gln Thr Glu Asn Ser Lys Lys Ser Asn Arg Thr Pro Tyr Gln 580 585 590 Tyr Phe Asn Ser Gly Glu Thr Lys Leu Ser Tyr Asn Gln Phe Lys Gln 595 600 605 His Val Leu Asn Leu Ser Lys Ser Lys Asp Arg Ile Ser Lys Lys Lys 610 615 620 Lys Glu Tyr Leu Leu Glu Glu Arg Asp Ile Asn Lys Tyr Glu Val Gln 625 630 635 640 Lys Glu Phe Ile Asn Arg Asn Leu Val Asp Thr Arg Tyr Ala Thr Arg 645 650 655 Glu Leu Thr Asn Tyr Leu Lys Ala Tyr Phe Ser Ala Asn Asp Met Asp 660 665 670 Val Lys Val Lys Thr Ile Asn Gly Ser Phe Thr Asp Tyr Leu Arg Lys 675 680 685 Val Trp Lys Phe Lys Lys Glu Arg Asn His Gly Tyr Lys His His Ala 690 695 700 Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Leu Phe Lys Glu Asn 705 710 715 720 Lys Lys Leu Lys Lys Ala Asn Ala Ile Leu Glu Gln Pro Ser Leu Asp 725 730 735 Asn Gly Lys Ser Asp Ala Thr Val Glu Asn Asp Asn Glu Tyr Val Glu 740 745 750 Thr Phe Ser Ile Pro Lys Gln Val Asn Asp Ile Lys Glu Phe Arg Asp 755 760 765 Phe Lys Phe Ser His Arg Val Asp Lys Lys Pro Asn Arg Gln Leu Ile 770 775 780 Asn Asp Thr Leu Tyr Ser Thr Arg Lys Ile Glu Asn His Thr Phe Ile 785 790 795 800 Val Ser Pro Ile Thr Asn Ile Tyr Ser Lys Asp Asn Asp Glu Leu Lys 805 810 815 Lys Lys Phe Asn Lys Asn Pro Glu Lys Phe Leu Met Tyr Gln His Asp 820 825 830 Pro Lys Thr Phe Glu Lys Leu Glu Val Ile Met Lys Gln Tyr Ala Asn 835 840 845 Glu Lys Asn Pro Leu Ala Lys Tyr His Glu Glu Thr Gly Glu Tyr Leu 850 855 860 Thr Lys Tyr Ser Lys Lys Asn Asn Gly Pro Ile Val Lys Thr Ile Lys 865 870 875 880 Val Leu Gly Asp Lys Val Gly Lys His Leu Asp Val Thr His Lys Tyr 885 890 895 Lys Tyr Ser Asn Ser Lys Ile Val Lys Lys Thr Ile Asn Pro Tyr Arg 900 905 910 Phe Asp Val Tyr Leu Thr Asp Lys Gly Tyr Lys Phe Ile Thr Ile Ser 915 920 925 Tyr Leu Asp Val Leu Lys Lys Asp Asn Tyr Tyr Tyr Ile Leu Lys Glu 930 935 940 Lys Tyr Glu Glu Leu Lys Ile Lys Lys Ser Ile Ser Asp Thr Asp Gln 945 950 955 960 Phe Ile Gly Ser Phe Tyr Tyr Asn Asp Leu Ile Lys Ile Asn Asp Gln 965 970 975 Ile Phe Lys Val Val Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu 980 985 990 Leu Asp Leu Leu Asp Ile Ser Tyr Lys Glu Tyr Cys Lys Ile Asn Asn 995 1000 1005 Ile Lys Thr Asn Arg Ile Ile Lys Gly Ile Thr Lys Lys Ile Thr 1010 1015 1020 Asn Ile Glu Lys Phe Ser Thr Asp Val Leu Gly Asn Leu Tyr Lys 1025 1030 1035 Ala His Ser Asn His Pro Gln Leu Ile Phe Lys Gln Arg Asp 1040 1045 1050 <210> 60 <211> 1072 <212> PRT <213> Bacillus sp. <220> <221> source <223> /note="Bacillus sp. APG08290.1" <400> 60 Met Ser Glu Leu Asp Tyr Arg Ile Gly Leu Asp Ile Gly Thr Asn Ser 1 5 10 15 Ile Gly Trp Gly Val Ile Glu Leu Phe Trp Asn Lys Asp Arg Glu Arg 20 25 30 Tyr Glu Lys Val Arg Ile Val Asp Lys Gly Val Arg Met Phe Asp Lys 35 40 45 Ala Glu Ile Pro Asn Lys Gly Ala Ser Leu Ala Glu Pro Arg Arg Ile 50 55 60 Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys Ser Gln Arg Lys Lys 65 70 75 80 Glu Ile Arg Asn Leu Leu Val Gln His Gly Met Ile Thr Gln Glu Glu 85 90 95 Leu Asp Leu Leu Tyr Pro Leu Ser Lys Lys Ser Ile Asp Ile Trp Asp 100 105 110 Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn His Leu Glu Trp Ala 115 120 125 Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly Phe Lys Ser Asn Arg 130 135 140 Lys Ser Glu Leu Lys Asp Ala Glu Thr Gly Lys Val Leu Ser Ser Ile 145 150 155 160 Gln Val Asn Glu Lys Arg Leu Phe Leu Tyr Arg Thr Val Gly Glu Met 165 170 175 Trp Ile Lys Asp Ala Glu Phe Ser Lys Tyr Asp Arg Arg Arg Asn Ser 180 185 190 Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala Asp Leu Glu Lys Glu 195 200 205 Ile Val Thr Leu Phe Glu Ala Gln Arg Lys Phe Gln Ser Ser Tyr Ala 210 215 220 Ser Lys Asn Leu Gln Glu Thr Tyr Leu Gln Ile Trp Ala His Gln Leu 225 230 235 240 Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys Val Gly Tyr Cys Ser 245 250 255 Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys Ala Thr Tyr Thr Phe 260 265 270 Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg Thr Arg Leu Gly Pro 275 280 285 Asp Phe Gln Pro Phe Thr Gln Glu Gln Lys Glu Ile Ile Leu Asp Lys 290 295 300 Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys Thr Ile Pro Glu Val 305 310 315 320 Ser Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu Asp Glu Thr Ile Gln 325 330 335 Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu Leu Lys Lys Ile Glu 340 345 350 Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr Glu Ile Lys Lys Val 355 360 365 Val Ala Asn Tyr Ala Glu Arg Thr Asn Glu Ala Phe Ser Thr Leu Asp 370 375 380 Tyr Asp Ala Ile Ala Tyr Ala Leu Thr Val Tyr Lys Thr Asp Lys Asp 385 390 395 400 Ile Arg Ser Tyr Leu Lys Lys Ser Asn Asn Leu Ser Lys Arg Cys Tyr 405 410 415 Asp Asp Gln Leu Ile Glu Glu Leu Phe Thr Leu Ser Tyr Thr Lys Phe 420 425 430 Gly His Leu Ser Phe Lys Ala Ile Asn His Val Leu Pro Ile Met Gln 435 440 445 Glu Gly Arg Thr Tyr Gln Glu Ala Ile His Gln Leu Gly Tyr Asp Thr 450 455 460 Thr Asn Leu Lys Lys Glu Asn Arg Ser Met Phe Leu Pro Leu Ile Pro 465 470 475 480 Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala Ile Thr Gln Ala Arg 485 490 495 Lys Val Val Asn Ala Ile Ile Arg Arg Tyr Gly Ser Pro Asn Ser Val 500 505 510 His Ile Glu Leu Ala Arg Glu Leu Ser Lys Ser His Asp Glu Arg Lys 515 520 525 Lys Ile Met Thr Ala His Asp Glu Asn Tyr Lys Lys Asn Lys Gly Ala 530 535 540 Ile Ser Ile Leu Ile Glu Asn Gly Ile Leu Asn Pro Thr Gly Tyr Asp 545 550 555 560 Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly Glu Arg Cys Ala Tyr 565 570 575 Ser Leu Lys Glu Ile Pro Pro Asp Thr Phe Phe Asn Glu Leu Lys Lys 580 585 590 Glu Arg Asn Gly Ser Pro Ile Leu Glu Val Asp His Ile Leu Pro Tyr 595 600 605 Ser Gln Ser Phe Ile Asp Ser Tyr His Asn Lys Val Leu Val Tyr Ser 610 615 620 Asp Glu Asn Arg Asn Lys Gly Asn Arg Ile Pro Tyr Thr Tyr Phe Leu 625 630 635 640 Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu Arg Tyr Val Arg Ser Asn 645 650 655 Lys Leu Phe Ser Lys Lys Lys Arg Glu Tyr Leu Leu Lys Lys Lys Thr Tyr 660 665 670 Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu Arg His Leu Asn Asp Thr 675 680 685 Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe Ile Glu Gln Asn Leu Gln 690 695 700 Phe Lys Glu Val Glu Val Asn Leu Arg Lys Lys Arg Val Gln Thr Val 705 710 715 720 Asn Gly Val Ile Thr Ala His Leu Arg Lys Arg Trp Gly Leu Glu Lys 725 730 735 Asn Arg Gln Glu Thr Tyr Leu His His Ala Met Asp Ala Ile Ile Val 740 745 750 Ala Cys Thr Asp His His Met Val Thr Arg Ile Thr Glu Tyr Tyr Gln 755 760 765 Ile Lys Glu Ser Asn Lys Ser Val Lys Lys Pro Tyr Phe Pro Met Pro 770 775 780 Trp Glu Gly Phe Arg Asp Glu Leu Leu Ser His Leu Ala Ser Gln Pro 785 790 795 800 Ile Ala Lys Lys Ile Ser Glu Glu Leu Lys Ala Gly Tyr Gln Ser Ser 805 810 815 Asp Tyr Ile Phe Val Ser Arg Met Pro Lys Arg Ser Val Thr Gly Ala 820 825 830 Ala His Asp Gln Thr Ile Arg Arg Lys Gly Gly Ile Asp Lys Lys Gly 835 840 845 Lys Thr Ile Ile Ile Lys Arg Val Arg Leu Lys Asp Ile Lys Phe Asp 850 855 860 Glu Asn Gly Asp Phe Lys Met Val Gly Lys Glu Gln Asp Leu Ala Thr 865 870 875 880 Tyr Glu Ala Ile Lys Gln Arg Tyr Leu Glu His Arg Lys Asn Ser Lys 885 890 895 Lys Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly 900 905 910 Asn Leu Ile Lys Arg Val Lys Ile Glu Gly Gln Thr Lys Ala Phe Val 915 920 925 Arg Glu Val Asn Gly Gly Val Ala Gln Asn Ser Asp Leu Val Arg Val 930 935 940 Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile Tyr Val 945 950 955 960 Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val Val Lys Ser Gly 965 970 975 Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser Phe Thr Phe Lys 980 985 990 Ser Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu Val Lys Gly Asn Glu 995 1000 1005 Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp Ile Asp Ser Asp Arg 1010 1015 1020 Leu Asn Phe Lys Asp Val Asn Lys Pro Ser Lys Gln Asn Glu Tyr 1025 1030 1035 Arg Tyr Ser Leu Lys Thr Ile Glu Asn Leu Glu Lys Tyr Glu Val 1040 1045 1050 Gly Val Leu Gly Asp Leu Arg Leu Val Lys Gln Glu Thr Arg Arg 1055 1060 1065 Ile Phe Asn Arg 1070 <210> 61 <211> 1072 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="nAPG08290.1" <400> 61 Met Ser Glu Leu Asp Tyr Arg Ile Gly Leu Ala Ile Gly Thr Asn Ser 1 5 10 15 Ile Gly Trp Gly Val Ile Glu Leu Phe Trp Asn Lys Asp Arg Glu Arg 20 25 30 Tyr Glu Lys Val Arg Ile Val Asp Lys Gly Val Arg Met Phe Asp Lys 35 40 45 Ala Glu Ile Pro Asn Lys Gly Ala Ser Leu Ala Glu Pro Arg Arg Ile 50 55 60 Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys Ser Gln Arg Lys Lys 65 70 75 80 Glu Ile Arg Asn Leu Leu Val Gln His Gly Met Ile Thr Gln Glu Glu 85 90 95 Leu Asp Leu Leu Tyr Pro Leu Ser Lys Lys Ser Ile Asp Ile Trp Asp 100 105 110 Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn His Leu Glu Trp Ala 115 120 125 Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly Phe Lys Ser Asn Arg 130 135 140 Lys Ser Glu Leu Lys Asp Ala Glu Thr Gly Lys Val Leu Ser Ser Ile 145 150 155 160 Gln Val Asn Glu Lys Arg Leu Phe Leu Tyr Arg Thr Val Gly Glu Met 165 170 175 Trp Ile Lys Asp Ala Glu Phe Ser Lys Tyr Asp Arg Arg Arg Asn Ser 180 185 190 Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala Asp Leu Glu Lys Glu 195 200 205 Ile Val Thr Leu Phe Glu Ala Gln Arg Lys Phe Gln Ser Ser Tyr Ala 210 215 220 Ser Lys Asn Leu Gln Glu Thr Tyr Leu Gln Ile Trp Ala His Gln Leu 225 230 235 240 Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys Val Gly Tyr Cys Ser 245 250 255 Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys Ala Thr Tyr Thr Phe 260 265 270 Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg Thr Arg Leu Gly Pro 275 280 285 Asp Phe Gln Pro Phe Thr Gln Glu Gln Lys Glu Ile Ile Leu Asp Lys 290 295 300 Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys Thr Ile Pro Glu Val 305 310 315 320 Ser Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu Asp Glu Thr Ile Gln 325 330 335 Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu Leu Lys Lys Ile Glu 340 345 350 Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr Glu Ile Lys Lys Val 355 360 365 Val Ala Asn Tyr Ala Glu Arg Thr Asn Glu Ala Phe Ser Thr Leu Asp 370 375 380 Tyr Asp Ala Ile Ala Tyr Ala Leu Thr Val Tyr Lys Thr Asp Lys Asp 385 390 395 400 Ile Arg Ser Tyr Leu Lys Lys Ser Asn Asn Leu Ser Lys Arg Cys Tyr 405 410 415 Asp Asp Gln Leu Ile Glu Glu Leu Phe Thr Leu Ser Tyr Thr Lys Phe 420 425 430 Gly His Leu Ser Phe Lys Ala Ile Asn His Val Leu Pro Ile Met Gln 435 440 445 Glu Gly Arg Thr Tyr Gln Glu Ala Ile His Gln Leu Gly Tyr Asp Thr 450 455 460 Thr Asn Leu Lys Lys Glu Asn Arg Ser Met Phe Leu Pro Leu Ile Pro 465 470 475 480 Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala Ile Thr Gln Ala Arg 485 490 495 Lys Val Val Asn Ala Ile Ile Arg Arg Tyr Gly Ser Pro Asn Ser Val 500 505 510 His Ile Glu Leu Ala Arg Glu Leu Ser Lys Ser His Asp Glu Arg Lys 515 520 525 Lys Ile Met Thr Ala His Asp Glu Asn Tyr Lys Lys Asn Lys Gly Ala 530 535 540 Ile Ser Ile Leu Ile Glu Asn Gly Ile Leu Asn Pro Thr Gly Tyr Asp 545 550 555 560 Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly Glu Arg Cys Ala Tyr 565 570 575 Ser Leu Lys Glu Ile Pro Pro Asp Thr Phe Phe Asn Glu Leu Lys Lys 580 585 590 Glu Arg Asn Gly Ser Pro Ile Leu Glu Val Asp His Ile Leu Pro Tyr 595 600 605 Ser Gln Ser Phe Ile Asp Ser Tyr His Asn Lys Val Leu Val Tyr Ser 610 615 620 Asp Glu Asn Arg Asn Lys Gly Asn Arg Ile Pro Tyr Thr Tyr Phe Leu 625 630 635 640 Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu Arg Tyr Val Arg Ser Asn 645 650 655 Lys Leu Phe Ser Lys Lys Lys Arg Glu Tyr Leu Leu Lys Lys Lys Thr Tyr 660 665 670 Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu Arg His Leu Asn Asp Thr 675 680 685 Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe Ile Glu Gln Asn Leu Gln 690 695 700 Phe Lys Glu Val Glu Val Asn Leu Arg Lys Lys Arg Val Gln Thr Val 705 710 715 720 Asn Gly Val Ile Thr Ala His Leu Arg Lys Arg Trp Gly Leu Glu Lys 725 730 735 Asn Arg Gln Glu Thr Tyr Leu His His Ala Met Asp Ala Ile Ile Val 740 745 750 Ala Cys Thr Asp His His Met Val Thr Arg Ile Thr Glu Tyr Tyr Gln 755 760 765 Ile Lys Glu Ser Asn Lys Ser Val Lys Lys Pro Tyr Phe Pro Met Pro 770 775 780 Trp Glu Gly Phe Arg Asp Glu Leu Leu Ser His Leu Ala Ser Gln Pro 785 790 795 800 Ile Ala Lys Lys Ile Ser Glu Glu Leu Lys Ala Gly Tyr Gln Ser Ser 805 810 815 Asp Tyr Ile Phe Val Ser Arg Met Pro Lys Arg Ser Val Thr Gly Ala 820 825 830 Ala His Asp Gln Thr Ile Arg Arg Lys Gly Gly Ile Asp Lys Lys Gly 835 840 845 Lys Thr Ile Ile Ile Lys Arg Val Arg Leu Lys Asp Ile Lys Phe Asp 850 855 860 Glu Asn Gly Asp Phe Lys Met Val Gly Lys Glu Gln Asp Leu Ala Thr 865 870 875 880 Tyr Glu Ala Ile Lys Gln Arg Tyr Leu Glu His Arg Lys Asn Ser Lys 885 890 895 Lys Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly 900 905 910 Asn Leu Ile Lys Arg Val Lys Ile Glu Gly Gln Thr Lys Ala Phe Val 915 920 925 Arg Glu Val Asn Gly Gly Val Ala Gln Asn Ser Asp Leu Val Arg Val 930 935 940 Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile Tyr Val 945 950 955 960 Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val Val Lys Ser Gly 965 970 975 Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser Phe Thr Phe Lys 980 985 990 Ser Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu Val Lys Gly Asn Glu 995 1000 1005 Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp Ile Asp Ser Asp Arg 1010 1015 1020 Leu Asn Phe Lys Asp Val Asn Lys Pro Ser Lys Gln Asn Glu Tyr 1025 1030 1035 Arg Tyr Ser Leu Lys Thr Ile Glu Asn Leu Glu Lys Tyr Glu Val 1040 1045 1050 Gly Val Leu Gly Asp Leu Arg Leu Val Lys Gln Glu Thr Arg Arg 1055 1060 1065 Ile Phe Asn Arg 1070 <210> 62 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG06646 Target 1" <400> 62 aatgagttta ggatttttct ttgaagccag ctatctatcc cattctctgc aaaagaataa 60 aaagt 65 <210> 63 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG06646 Target 2" <400> 63 attaatgagt ttaggatttt tctttgaagc cagctatcta tcccattctc tgcaaaagaa 60 65 <210> 64 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG06646 Target 3" <400> 64 gcattaatga gtttaggatt tttctttgaa gccagctatc tatcccattc tctgcaaaag 60 aataa 65 <210> 65 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG06646 Target 4" <400> 65 aagggcatta atgagtttag gatttttctt tgaagccagc tatctatccc attctctgca 60 aaaga 65 <210> 66 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG06646 Target 5" <400> 66 gaagggcatt aatgagttta ggatttttct ttgaagccag ctatctatcc cattctctgc 60 65 <210> 67 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG06646 Target 6" <400> 67 cgaagggcat taatgagttt aggatttttc tttgaagcca gctatctatc ccattctctg 60 caaaa 65 <210> 68 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG09882 Target 1" <400> 68 gagtttagga tttttctttg aagccagcta tctatcccat tctctgcaaa agaataaaaa 60 gtggg 65 <210> 69 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG09882 Target 2" <400> 69 tgagtttagg atttttcttt gaagccagct atctatccca ttctctgcaa aagaataaaa 60 agtgg 65 <210> 70 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG09882 Target 3" <400> 70 atgagtttag gatttttctt tgaagccagc tatctatccc attctctgca aaagaataaa 60 aagtg 65 <210> 71 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG09882 Target 4" <400> 71 agggcattaa tgagtttagg atttttcttt gaagccagct atctatccca ttctctgcaa 60 aagaa 65 <210> 72 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG00969 Target 1" <400> 72 gtttaggatt tttctttgaa gccagctatc tatcccattc tctgcaaaag aataaaaagt 60 gggac 65 <210> 73 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG00969 Target 2" <400> 73 agtttaggat ttttctttga agccagctat ctatcccatt ctctgcaaaa gaataaaaag 60 tggga 65 <210> 74 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG03850 Target 1" <400> 74 ggatttttct ttgaagccag ctatctatcc cattctctgc aaaagaataa aaagtgggac 60 <210> 75 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG03850 Target 2" <400> 75 agtttaggat ttttctttga agccagctat ctatcccatt ctctgcaaaa gaataaaaag 60 <210> 76 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG07433.1 Target 1" <400> 76 gaagggcatt aatgagttta ggatttttct ttgaagccag ctatctatcc cattctctgc 60 65 <210> 77 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG09748Target 1" <400> 77 gtcccacttt ttattctttt gcagagaatg ggatagatag ctggcttcaa agaaaaatcc 60 <210> 78 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG07553 Target 1" <400> 78 agtttaggat ttttctttga agccagctat ctatcccatt ctctgcaaaa gaataaaaag 60 <210> 79 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG05586 Target 1" <400> 79 tttaggattt ttctttgaag ccagctatct atcccattct ctgcaaaaga ataaaaagtg 60 <210> 80 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG06646 Target 1" <400> 80 ttgaagccag ctatctatcc cattc 25 <210> 81 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG06646 Target 2" <400> 81 tctttgaagc cagctatcta tccca 25 <210> 82 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG06646 Target 3" <400> 82 tttctttgaa gccagctatc tatcc 25 <210> 83 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG06646 Target 4" <400> 83 gatttttctt tgaagccagc tatct 25 <210> 84 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG06646 Target 5" <400> 84 ggatttttct ttgaagccag ctatc 25 <210> 85 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG06646 Target 6" <400> 85 aggatttttc tttgaagcca gctat 25 <210> 86 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG09882 Target 1" <400> 86 aagccagcta tctatcccat tctct 25 <210> 87 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG09882 Target 2" <400> 87 gaagccagct atctatccca ttctc 25 <210> 88 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG09882 Target 3" <400> 88 tgaagccagc tatctatccc attct 25 <210> 89 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG09882 Target 4" <400> 89 atttttcttt gaagccagct atcta 25 <210> 90 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG00969 Target 1" <400> 90 gccagctatc tatcccattc tctgc 25 <210> 91 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG00969 Target 2" <400> 91 agccagctat ctatcccatt ctctg 25 <210> 92 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG03850 Target 1" <400> 92 ctatctatcc cattctctgc 20 <210> 93 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG03850 Target 2" <400> 93 agccagctat ctatcccatt 20 <210> 94 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG07433.1 Target 1" <400> 94 ggatttttct ttgaagccag ctatc 25 <210> 95 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG09748Target 1" <400> 95 gcagagaatg ggagagatag 20 <210> 96 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG07553 Target 1" <400> 96 agccagctat ctatcccatt 20 <210> 97 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF E60X nAPG05586 Target 1" <400> 97 ccagctatct atcccattct 20 <210> 98 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF E60X nAPG06646 Target 1 sgRNA" <400> 98 uugaagccag cuaucuaucc cauucgccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 99 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF E60X nAPG06646 Target 2 sgRNA" <400> 99 ucuuugaagc cagcuaucua ucccagccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 100 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF E60X nAPG06646 Target 3 sgRNA" <400> 100 uuucuuugaa gccagcuauc uauccgccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 101 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF E60X nAPG06646 Target 4 sgRNA" <400> 101 gauuuuucuu ugaagccagc uaucugccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 102 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF E60X nAPG06646 Target 5 sgRNA" <400> 102 ggauuuuucu uugaagccag cuaucgccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 103 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF E60X nAPG06646 Target 6 sgRNA" <400> 103 aggauuuuuc uuugaagcca gcuaugccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 104 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF E60X nAPG09882 Target 1 sgRNA" <400> 104 aagccagcua ucuaucccau ucucuguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 105 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF E60X nAPG09882 Target 2 sgRNA" <400> 105 gaagccagcu aucuauccca uucucguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 106 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF E60X nAPG09882 Target 3 sgRNA" <400> 106 ugaagccagc uaucuauccc auucuguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 107 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF E60X nAPG09882 Target 4 sgRNA" <400> 107 auuuuucuuu gaagccagcu aucuaguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 108 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF E60X nAPG00969 Target 1 sgRNA" <400> 108 gccagcuauc uaucccauuc ucugcguuuu aguacucugu gaaagcacag aaucuacuaa 60 118 <210> 109 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF E60X nAPG00969 Target 2 sgRNA" <400> 109 agccagcuau cuaucccauu cucugguuuu aguacucugu gaaagcacag aaucuacuaa 60 118 <210> 110 <211> 163 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF E60X nAPG03850 Target 1 sgRNA" <400> 110 cuaucuaucc cauucucugc gcuauaguuc cauaagaaaa aaguuucuua aguuacuaua 60 guaagggcaa ugacccgugg cguuugggga ucgccuuauc cugguaugga uauucuccccc 120 augugaaaag caccuaagca uagcgcuaug gugcuuuuau uuu 163 <210> 111 <211> 163 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF E60X nAPG03850 Target 2 sgRNA" <400> 111 agccagcuau cuaucccauu gcuauaguuc cauaagaaaa aaguuucuua aguuacuaua 60 guaagggcaa ugacccgugg cguuugggga ucgccuuauc cugguaugga uauucuccccc 120 augugaaaag caccuaagca uagcgcuaug gugcuuuuau uuu 163 <210> 112 <211> 135 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF E60X nAPG07433.1 Target 1 sgRNA" <400> 112 ggauuuuucu uugaagccag cuaucgucau aguuccauua aagccaaaag uggcuuugau 60 120 uucuccccau uuauu 135 <210> 113 <211> 135 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF E60X nAPG09748Target 1 sgRNA" <400> 113 cgacgguuag aggccguaug ucgauuugcu uuaauuucgu gcgugugcau ugucguccuc 60 cauuacaggg cggcuaccac gaauagccac gaaguaaaag cuucguggcu agcacgcaga 120 gaaugggaua gauag 135 <210> 114 <211> 151 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF E60X nAPG07553 Target 1 sgRNA" <400> 114 agccagcuau cuaucccauu gcuauaguuc cauaagaaag cuuaaguuac uauaguaagg 60 gcaaugaccc guggcguuug gggaucgccu cauccauuac ggauauucuc cccaugugaa 120 aagcaccuaa gcauaaggcu aaggugcuuu u 151 <210> 115 <211> 110 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF E60X nAPG05586 Target 1 sgRNA" <400> 115 ccagcuaucu aucccauucu guuauuguac ucucauuaaa aaguuauuga gaaucuacaa 60 uaauaaggca ucuugccgaa uuuaccgccc uacauaugua gggcgguuuu 110 <210> 116 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG06646 Target 1" <400> 116 cgttgacctc cactcagtgt gattccacct tctcaaagaa ctatattgtc tttctctgca 60 act 65 <210> 117 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG06646 Target 2" <400> 117 gacctccact cagtgtgatt ccaccttctc aaagaactat attgtctttc tctgcaaact 60 tggag 65 <210> 118 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG06646 Target 3" <400> 118 cctccactca gtgtgattcc accttctcaa agaactatat tgtctttctc tgcaaacttg 60 gagat 65 <210> 119 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG06646 Target 4" <400> 119 ccactcagtg tgattccacc ttctcaaaga actatattgt ctttctctgc aaacttggag 60 atgtc 65 <210> 120 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG09882 Target 1" <400> 120 tcttgctcgt tgacctccac tcagtgtgat tccaccttct caaagaacta tattgtcttt 60 ctctg 65 <210> 121 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG09882 Target 2" <400> 121 ttgctcgttg acctccactc agtgtgattc caccttctca aagaactata ttgtctttct 60 ctgca 65 <210> 122 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG09882 Target 3" <400> 122 cactcagtgt gattccacct tctcaaagaa ctatattgtc tttctctgca aacttggaga 60 tgtcc 65 <210> 123 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG03850 Target 1" <400> 123 tgacctccac tcagtgtgat tccaccttct caaagaacta tattgtcttt ctctgcaaac 60 <210> 124 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG03850 Target 2" <400> 124 tcagtgtgat tccaccttct caaagaacta tattgtcttt ctctgcaaac ttggagatgt 60 <210> 125 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG09748 Target 1" <400> 125 agagaaagac aatatagttc tttgagaagg tggaatcaca ctgagtggag gtcaacgagc 60 <210> 126 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG07553 Target 1" <400> 126 tcagtgtgat tccaccttct caaagaacta tattgtcttt ctctgcaaac ttggagatgt 60 <210> 127 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG05586 Target 1" <400> 127 cgttgacctc cactcagtgt gattccacct tctcaaagaa ctatattgtc tttctctgca 60 <210> 128 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG06646 Target 1" <400> 128 gattccacct tctcaaagaa ctata 25 <210> 129 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG06646 Target 2" <400> 129 ccaccttctc aaagaactat attgt 25 <210> 130 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG06646 Target 3" <400> 130 accttctcaa agaactatat tgtct 25 <210> 131 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG06646 Target 4" <400> 131 ttctcaaaga actatattgt ctttc 25 <210> 132 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG09882 Target 1" <400> 132 tcagtgtgat tccaccttct caaag 25 <210> 133 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG09882 Target 2" <400> 133 agtgtgattc caccttctca aagaa 25 <210> 134 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG09882 Target 3" <400> 134 tctcaaagaa ctatattgtc tttct 25 <210> 135 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG03850 Target 1" <400> 135 tccaccttct caaagaacta 20 <210> 136 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG03850 Target 2" <400> 136 caaagaacta tattgtcttt 20 <210> 137 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG09748 Target 1" <400> 137 tttgagaagg tggaatcaca 20 <210> 138 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG07553 Target 1" <400> 138 caaagaacta tattgtcttt 20 <210> 139 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF G542X nAPG05586 Target 1" <400> 139 gattccacct tctcaaagaa 20 <210> 140 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF G542X nAPG06646 Target 1 sgRNA" <400> 140 gauuccaccu ucucaaagaa cuauagccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 141 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF G542X nAPG06646 Target 2 sgRNA" <400> 141 ccaccuucuc aaagaacuau auugugccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 142 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF G542X nAPG06646 Target 3 sgRNA" <400> 142 accuucucaa agaacuauau ugucugccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 143 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF G542X nAPG06646 Target 4 sgRNA" <400> 143 uuucaaaga acuauauugu cuuucgccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 144 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF G542X nAPG09882 Target 1 sgRNA" <400> 144 ucagugugau uccaccuucu caaagguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 145 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF G542X nAPG09882 Target 2 sgRNA" <400> 145 agugugauuc caccuucuca aagaaguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 146 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF G542X nAPG09882 Target 3 sgRNA" <400> 146 ucucaaagaa cuauauuguc uuucuguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 147 <211> 163 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF G542X nAPG03850 Target 1 sgRNA" <400> 147 uccaccuucu caaagaacua gcuauaguuc cauaagaaaa aaguuucuua aguuacuaua 60 guaagggcaa ugacccgugg cguuugggga ucgccuuauc cugguaugga uauucuccccc 120 augugaaaag caccuaagca uagcgcuaug gugcuuuuau uuu 163 <210> 148 <211> 163 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF G542X nAPG03850 Target 2 sgRNA" <400> 148 caaagaacua uauugucuuu gcuauaguuc cauaagaaaa aaguuucuua aguuacuaua 60 guaagggcaa ugacccgugg cguuugggga ucgccuuauc cugguaugga uauucuccccc 120 augugaaaag caccuaagca uagcgcuaug gugcuuuuau uuu 163 <210> 149 <211> 135 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF G542X nAPG09748 Target 1 sgRNA" <400> 149 cgacgguuag aggccguaug ucgauuugcu uuaauuucgu gcgugugcau ugucguccuc 60 cauuacaggg cggcuaccac gaauagccac gaaguaaaag cuucguggcu agcacuuuga 120 gaagguggaa ucaca 135 <210> 150 <211> 151 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF G542X nAPG07553 Target 1 sgRNA" <400> 150 caaagaacua uauugucuuu gcuauaguuc cauaagaaag cuuaaguuac uauaguaagg 60 gcaaugaccc guggcguuug gggaucgccu cauccauuac ggauauucuc cccaugugaa 120 aagcaccuaa gcauaaggcu aaggugcuuu u 151 <210> 151 <211> 110 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF G542X nAPG05586 Target 1 sgRNA" <400> 151 gauuccaccu ucucaaagaa guuauuguac ucucauaaa aaguuauuga gaaucuacaa 60 uaauaaggca ucuugccgaa uuuaccgccc uacauaugua gggcgguuuu 110 <210> 152 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG09882 Target 1" <400> 152 gatattttct ttaatggtgc caggcataat ccaggaaaac taagaacaga atgaaattct 60 tccac 65 <210> 153 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG09882 Target 2" <400> 153 atattttctt taatggtgcc aggcataatc caggaaaact aagaacagaa tgaaattctt 60 ccact 65 <210> 154 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG09882 Target 3" <400> 154 ttttctttaa tggtgccagg cataatccag gaaaactaag aacagaatga aattcttcca 60 ctgtg 65 <210> 155 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG09882 Target 4" <400> 155 tttctttaat ggtgccaggc ataatccagg aaaactaaga acagaatgaa attcttccac 60 tgtgc 65 <210> 156 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG09882 Target 5" <400> 156 ttctttaatg gtgccaggca taatccagga aaactaagaa cagaatgaaa ttcttccact 60 gtgct 65 <210> 157 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG09748 Target 1" <400> 157 taagcacagt ggaagaattt cattctgttc ttagttttcc tggattatgc ctggcaccat 60 <210> 158 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG09748 Target 2" <400> 158 aagcacagtg gaagaatttc attctgttct tagttttcct ggattatgcc tggcaccatt 60 <210> 159 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG09748 Target 3" <400> 159 acagtggaag aatttcattc tgttcttagt tttcctggat tatgcctggc accattaaag 60 <210> 160 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG09748 Target 4" <400> 160 ggaagaattt cattctgttc ttagttttcc tggattatgc ctggcaccat taaagaaaat 60 <210> 161 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG00969 Target 1" <400> 161 gatattttct ttaatggtgc caggcataat ccaggaaaac taagaacaga atgaaattct 60 tccac 65 <210> 162 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG00969 Target 2" <400> 162 ttctttaatg gtgccaggca taatccagga aaactaagaa cagaatgaaa ttcttccact 60 gtgct 65 <210> 163 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG06646 Target 1" <400> 163 tttaatggtg ccaggcataa tccaggaaaa ctaagaacag aatgaaattc ttccactgtg 60 cttaa 65 <210> 164 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG06646 Target 2" <400> 164 aatggtgcca ggcataatcc aggaaaacta agaacagaat gaaattcttc cactgtgctt 60 aattt 65 <210> 165 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG01604 Target 1" <400> 165 ttctttaatg gtgccaggca taatccagga aaactaagaa cagaatgaaa ttcttccact 60 <210> 166 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG01604 Target 2" <400> 166 ttaatggtgc caggcataat ccaggaaaac taagaacaga atgaaattct tccactgtgc 60 <210> 167 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG03850 Target 1" <400> 167 ctttaatggt gccaggcata atccaggaaa actaagaaca gaatgaaatt cttccactgt 60 <210> 168 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG07553 Target 1" <400> 168 ctttaatggt gccaggcata atccaggaaa actaagaaca gaatgaaatt cttccactgt 60 <210> 169 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG09882 Target 1" <400> 169 caggcataat ccaggaaaac taaga 25 <210> 170 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG09882 Target 2" <400> 170 aggcataatc caggaaaact aagaa 25 <210> 171 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG09882 Target 3" <400> 171 cataatccag gaaaactaag aacag 25 <210> 172 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG09882 Target 4" <400> 172 ataatccagg aaaactaaga acaga 25 <210> 173 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG09882 Target 5" <400> 173 taatccagga aaactaagaa cagaa 25 <210> 174 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG09748 Target 1" <400> 174 cattctgttc ttagttttcc 20 <210> 175 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG09748 Target 2" <400> 175 attctgttct tagttttcct 20 <210> 176 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG09748 Target 3" <400> 176 tgttcttagt tttcctggat 20 <210> 177 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG09748 Target 4" <400> 177 ttagttttcc tggattatgc 20 <210> 178 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG00969 Target 1" <400> 178 caggcataat ccaggaaaac taaga 25 <210> 179 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG00969 Target 2" <400> 179 taatccagga aaactaagaa cagaa 25 <210> 180 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG06646 Target 1" <400> 180 tccaggaaaa ctaagaacag aatga 25 <210> 181 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG06646 Target 2" <400> 181 aggaaaacta agaacagaat gaaat 25 <210> 182 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG01604 Target 1" <400> 182 taatccagga aaactaagaa 20 <210> 183 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG01604 Target 2" <400> 183 ccaggaaaac taagaacaga 20 <210> 184 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG03850 Target 1" <400> 184 atccaggaaa actaagaaca 20 <210> 185 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF Q493X nAPG07553 Target 1" <400> 185 atccaggaaa actaagaaca 20 <210> 186 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF Q493X nAPG09882 Target 1 sgRNA" <400> 186 caggcauaau ccaggaaaac uaagaguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 187 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF Q493X nAPG09882 Target 2 sgRNA" <400> 187 aggcauaauc caggaaaacu aagaaguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 188 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF Q493X nAPG09882 Target 3 sgRNA" <400> 188 cauaauccag gaaaacuaag aacagguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 189 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF Q493X nAPG09882 Target 4 sgRNA" <400> 189 auaauccagg aaaacuaaga acagaguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 190 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF Q493X nAPG09882 Target 5 sgRNA" <400> 190 uaauccagga aaacuaagaa cagaaguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 191 <211> 135 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF Q493X nAPG09748 Target 1 sgRNA" <400> 191 cgacgguuag aggccguaug ucgauuugcu uuaauuucgu gcgugugcau ugucguccuc 60 cauuacaggg cggcuaccac gaauagccac gaaguaaaag cuucguggcu agcaccauuc 120 135 <210> 192 <211> 135 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF Q493X nAPG09748 Target 2 sgRNA" <400> 192 cgacgguuag aggccguaug ucgauuugcu uuaauuucgu gcgugugcau ugucguccuc 60 cauuacaggg cggcuaccac gaauagccac gaaguaaaag cuucguggcu agcacauucu 120 guucuuaguu uuccu 135 <210> 193 <211> 135 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF Q493X nAPG09748 Target 3 sgRNA" <400> 193 cgacgguuag aggccguaug ucgauuugcu uuaauuucgu gcgugugcau ugucguccuc 60 cauuacaggg cggcuaccac gaauagccac gaaguaaaag cuucguggcu agcacuguuc 120 uuaguuuucc uggau 135 <210> 194 <211> 135 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF Q493X nAPG09748 Target 4 sgRNA" <400> 194 cgacgguuag aggccguaug ucgauuugcu uuaauuucgu gcgugugcau ugucguccuc 60 cauuacaggg cggcuaccac gaauagccac gaaguaaaag cuucguggcu agcacuuagu 120 uuuccuggau uaugc 135 <210> 195 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF Q493X nAPG00969 Target 1 sgRNA" <400> 195 caggcauaau ccaggaaaac uaagaguuuu aguacucugu gaaagcacag aaucuacuaa 60 118 <210> 196 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF Q493X nAPG00969 Target 2 sgRNA" <400> 196 uaauccagga aaacuaagaa cagaaguuuu aguacucugu gaaagcacag aaucuacuaa 60 118 <210> 197 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF Q493X nAPG06646 Target 1 sgRNA" <400> 197 uccaggaaaa cuaagaacag aaugagccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 198 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF Q493X nAPG06646 Target 2 sgRNA" <400> 198 aggaaaacua agaacagaau gaaaugccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 199 <211> 105 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF Q493X nAPG01604 Target 1 sgRNA" <400> 199 uaauccagga aaacuaagaa guuuuaguac ucuguaaaaa guuacagaau cuacuaaaac 60 aaggcaaaau gccguguuua ucucgucaac uuguuggcga gauuu 105 <210> 200 <211> 105 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF Q493X nAPG01604 Target 2 sgRNA" <400> 200 ccaggaaaac uaagaacaga guuuuaguac ucuguaaaaa guuacagaau cuacuaaaac 60 aaggcaaaau gccguguuua ucucgucaac uuguuggcga gauuu 105 <210> 201 <211> 163 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF Q493X nAPG03850 Target 1 sgRNA" <400> 201 auccaggaaa acuaagaaca gcuauaguuc cauaagaaaa aaguuucuua aguuacuaua 60 guaagggcaa ugacccgugg cguuugggga ucgccuuauc cugguaugga uauucuccccc 120 augugaaaag caccuaagca uagcgcuaug gugcuuuuau uuu 163 <210> 202 <211> 151 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF Q493X nAPG07553 Target 1 sgRNA" <400> 202 auccaggaaa acuaagaaca gcuauaguuc cauaagaaag cuuaaguuac uauaguaagg 60 gcaaugaccc guggcguuug gggaucgccu cauccauuac ggauauucuc cccaugugaa 120 aagcaccuaa gcauaaggcu aaggugcuuu u 151 <210> 203 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG06646 Target 1" <400> 203 ccaataatta gttattcacc ttgctaaaga aattcttgct cattgacctc cactcagtgt 60 gattc 65 <210> 204 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG06646 Target 2" <400> 204 caataattag ttattcacct tgctaaagaa attcttgctc attgacctcc actcagtggg 60 attcc 65 <210> 205 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG06646 Target 3" <400> 205 ataattagtt attcaccttg ctaaagaaat tcttgctcat tgacctccac tcagtgtgat 60 tccac 65 <210> 206 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG06646 Target 4" <400> 206 aattagttat tcaccttgct aaagaaattc ttgctcattg acctccactc agtgtgattc 60 cacct 65 <210> 207 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG06646 Target 5" <400> 207 tcaccttgct aaagaaattc ttgctcattg acctccactc agtgtgattc caccttctcc 60 aagaa 65 <210> 208 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG06646 Target 6" <400> 208 caccttgcta aagaaattct tgctcattga cctccactca gtgtgattcc accttctcca 60 agaac 65 <210> 209 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG06646 Target 7" <400> 209 ccttgctaaa gaaattcttg ctcattgacc tccactcagt gtgattccac cttctccaag 60 aacta 65 <210> 210 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG07433.1 Target 1" <400> 210 ccaataatta gttattcacc ttgctaaaga aattcttgct cattgacctc cactcagtgt 60 gattc 65 <210> 211 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG07433.1 Target 2" <400> 211 tcaccttgct aaagaaattc ttgctcattg acctccactc agtgtgattc caccttctcc 60 aagaa 65 <210> 212 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG07433.1 Target 3" <400> 212 ccttgctaaa gaaattcttg ctcattgacc tccactcagt gtgattccac cttctccaag 60 aacta 65 <210> 213 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG09882 Target 1" <400> 213 aataattagt tattcacctt gctaaagaaa ttcttgctca ttgacctcca ctcagtgtga 60 tcca 65 <210> 214 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG09882 Target 2" <400> 214 attagttat caccttgcta aagaaattct tgctcattga cctccactca gtgtgattcc 60 acctt 65 <210> 215 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG09882 Target 3" <400> 215 tattcacctt gctaaagaaa ttcttgctca ttgacctcca ctcagtgtga ttccaccttc 60 tccaa 65 <210> 216 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG03850 Target 1" <400> 216 tattcacctt gctaaagaaa ttcttgctca ttgacctcca ctcagtgtga ttccaccttc 60 <210> 217 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG03850 Target 2" <400> 217 ttcaccttgc taaagaaatt cttgctcatt gacctccact cagtgtgatt ccaccttctc 60 <210> 218 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG03850 Target 3" <400> 218 caccttgcta aagaaattct tgctcattga cctccactca gtgtgattcc accttctcca 60 <210> 219 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG06646 Target 1" <400> 219 ttgctaaaga aattcttgct cattg 25 <210> 220 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG06646 Target 2" <400> 220 tgctaaagaa attcttgctc attga 25 <210> 221 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG06646 Target 3" <400> 221 ctaaagaaat tcttgctcat tgacc 25 <210> 222 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG06646 Target 4" <400> 222 aaagaaattc ttgctcattg acctc 25 <210> 223 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG06646 Target 5" <400> 223 ttgctcattg acctccactc agtgt 25 <210> 224 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG06646 Target 6" <400> 224 tgctcattga cctccactca gtgtg 25 <210> 225 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG06646 Target 7" <400> 225 ctcattgacc tccactcagt gtgat 25 <210> 226 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG07433.1 Target 1" <400> 226 ttgctaaaga aattcttgct cattg 25 <210> 227 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG07433.1 Target 2" <400> 227 ttgctcattg acctccactc agtgt 25 <210> 228 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG07433.1 Target 3" <400> 228 ctcattgacc tccactcagt gtgat 25 <210> 229 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG09882 Target 1" <400> 229 gctaaagaaa ttcttgctca ttgac 25 <210> 230 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG09882 Target 2" <400> 230 aagaaattct tgctcattga cctcc 25 <210> 231 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG09882 Target 3" <400> 231 ttcttgctca ttgacctcca ctcag 25 <210> 232 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG03850 Target 1" <400> 232 ttcttgctca ttgacctcca 20 <210> 233 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG03850 Target 2" <400> 233 cttgctcatt gacctccact 20 <210> 234 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R553X nAPG03850 Target 3" <400> 234 tgctcattga cctccactca 20 <210> 235 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R553X nAPG06646 Target 1 sgRNA" <400> 235 uugcuaaaga aauucuugcu cauuggccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 236 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R553X nAPG06646 Target 2 sgRNA" <400> 236 ugcuaaagaa auucuugcuc auugagccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 237 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R553X nAPG06646 Target 3 sgRNA" <400> 237 cuaaagaaau ucuugcucau ugaccgccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 238 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R553X nAPG06646 Target 4 sgRNA" <400> 238 aaagaaauuc uugcucauug accucgccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 239 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R553X nAPG06646 Target 5 sgRNA" <400> 239 uugcucauug accuccacuc agugugccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 240 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R553X nAPG06646 Target 6 sgRNA" <400> 240 ugcucauuga ccuccacuca guguggccau aauuccuug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 241 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R553X nAPG06646 Target 7 sgRNA" <400> 241 cucauugacc uccacucagu gugaugccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 242 <211> 135 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R553X nAPG07433.1 Target 1 sgRNA" <400> 242 uugcuaaaga aauucuugcu cauuggucau aguuccauua aagccaaaag uggcuuugau 60 120 uucuccccau uuauu 135 <210> 243 <211> 135 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R553X nAPG07433.1 Target 2 sgRNA" <400> 243 uugcucauug accuccacuc agugugucau aguuccauua aagccaaaag uggcuuugau 60 120 uucuccccau uuauu 135 <210> 244 <211> 135 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R553X nAPG07433.1 Target 3 sgRNA" <400> 244 cucauugacc uccacucagu gugaugucau aguuccauua aagccaaaag uggcuuugau 60 120 uucuccccau uuauu 135 <210> 245 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R553X nAPG09882 Target 1 sgRNA" <400> 245 gcuaaagaaa uucuugcuca uugacguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 246 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R553X nAPG09882 Target 2 sgRNA" <400> 246 aagaaauucu ugcucauuga ccuccguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 247 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R553X nAPG09882 Target 3 sgRNA" <400> 247 uucuugcuca uugaccucca cucagguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 248 <211> 163 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R553X nAPG03850 Target 1 sgRNA" <400> 248 uucuugcuca uugaccucca gcuauaguuc cauaagaaaa aaguuucuua aguuacuaua 60 guaagggcaa ugacccgugg cguuugggga ucgccuuauc cugguaugga uauucuccccc 120 augugaaaag caccuaagca uagcgcuaug gugcuuuuau uuu 163 <210> 249 <211> 163 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R553X nAPG03850 Target 2 sgRNA" <400> 249 60 guaagggcaa ugacccgugg cguuugggga ucgccuuauc cugguaugga uauucuccccc 120 augugaaaag caccuaagca uagcgcuaug gugcuuuuau uuu 163 <210> 250 <211> 163 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R553X nAPG03850 Target 3 sgRNA" <400> 250 ugcucauuga ccuccacuca gcuauaguuc cauaagaaaa aaguuucuua aguuacuaua 60 guaagggcaa ugacccgugg cguuugggga ucgccuuauc cugguaugga uauucuccccc 120 augugaaaag caccuaagca uagcgcuaug gugcuuuuau uuu 163 <210> 251 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG09882 Target 1" <400> 251 ggtttacctt ctgttggcat gtcaatgaac ttaaagactc agctcacaga tcgcatctga 60 aataa 65 <210> 252 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG09882 Target 2" <400> 252 accttctgtt ggcatgtcaa tgaacttaaa gactcagctc acagatcgca tctgaaataa 60 aaata 65 <210> 253 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG09882 Target 3" <400> 253 ctgttggcat gtcaatgaac ttaaagactc agctcacaga tcgcatctga aataaaaata 60 acaac 65 <210> 254 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG09882 Target 4" <400> 254 tgttggcatg tcaatgaact taaagactca gctcacagat cgcatctgaa ataaaaataa 60 caaca 65 <210> 255 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG09882 Target 5" <400> 255 gttggcatgt caatgaactt aaagactcag ctcacagatc gcatctgaaa taaaaataac 60 aacat 65 <210> 256 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG06646 Target 1" <400> 256 tttaccttct gttggcatgt caatgaactt aaagactcag ctcacagatc gcatctgaaa 60 65 <210> 257 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG06646 Target 2" <400> 257 taccttctgt tggcatgtca atgaacttaa agactcagct cacagatcgc atctgaaata 60 65 <210> 258 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG06646 Target 3" <400> 258 tggcatgtca atgaacttaa agactcagct cacagatcgc atctgaaata aaaataacaa 60 <210> 259 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG03850 Target 1" <400> 259 taccttctgt tggcatgtca atgaacttaa agactcagct cacagatcgc atctgaaata 60 <210> 260 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG03850 Target 2" <400> 260 ttctgttggc atgtcaatga acttaaagac tcagctcaca gatcgcatct gaaataaaaa 60 <210> 261 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG03850 Target 3" <400> 261 tggcatgtca atgaacttaa agactcagct cacagatcgc atctgaaata aaaataacaa 60 <210> 262 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG05586 Target 1" <400> 262 ttaccttctg ttggcatgtc aatgaactta aagactcagc tcacagatcg catctgaaat 60 <210> 263 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG05586 Target 2" <400> 263 ctgttggcat gtcaatgaac ttaaagactc agctcacaga tcgcatctga aataaaaata 60 <210> 264 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG05586 Target 3" <400> 264 tgtcaatgaa cttaaagact cagctcacag atcgcatctg aaataaaaat aacaacattt 60 <210> 265 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG00969 Target 1" <400> 265 ggtttacctt ctgttggcat gtcaatgaac ttaaagactc agctcacaga tcgcatctga 60 aataa 65 <210> 266 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG00969 Target 2" <400> 266 gttggcatgt caatgaactt aaagactcag ctcacagatc gcatctgaaa taaaaataac 60 aacat 65 <210> 267 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG07553 Target 1" <400> 267 tggcatgtca atgaacttaa agactcagct cacagatcgc atctgaaata aaaataacaa 60 <210> 268 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG01604 Target 1" <400> 268 gcatgtcaat gaacttaaag actcagctca cagatcgcat ctgaaataaa aataacaaca 60 <210> 269 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG09882 Target 1" <400> 269 gtcaatgaac ttaaagactc agctc 25 <210> 270 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG09882 Target 2" <400> 270 tgaacttaaa gactcagctc acaga 25 <210> 271 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG09882 Target 3" <400> 271 ttaaagactc agctcacaga tcgca 25 <210> 272 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG09882 Target 4" <400> 272 taaagactca gctcacagat cgcat 25 <210> 273 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG09882 Target 5" <400> 273 aaagactcag ctcacagatc gcatc 25 <210> 274 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG06646 Target 1" <400> 274 caatgaactt aaagactcag ctcac 25 <210> 275 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG06646 Target 2" <400> 275 atgaacttaa agactcagct cacag 25 <210> 276 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG06646 Target 3" <400> 276 aacttaaaga ctcagctcac agatc 25 <210> 277 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG03850 Target 1" <400> 277 atgaacttaa agactcagct 20 <210> 278 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG03850 Target 2" <400> 278 acttaaagac tcagctcaca 20 <210> 279 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG03850 Target 3" <400> 279 agactcagct cacagatcgc 20 <210> 280 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG05586 Target 1" <400> 280 aatgaactta aagactcagc 20 <210> 281 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG05586 Target 2" <400> 281 ttaaagactc agctcacaga 20 <210> 282 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG05586 Target 3" <400> 282 cagctcacag atcgcatctg 20 <210> 283 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG00969 Target 1" <400> 283 gtcaatgaac ttaaagactc agctc 25 <210> 284 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG00969 Target 2" <400> 284 aaagactcag ctcacagatc gcatc 25 <210> 285 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG07553 Target 1" <400> 285 agactcagct cacagatcgc 20 <210> 286 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF R1162X nAPG01604 Target 1" <400> 286 actcagctca cagatcgcat 20 <210> 287 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R1162X nAPG09882 Target 1 sgRNA" <400> 287 gucaaugaac uuaaagacuc agcucguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 288 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R1162X nAPG09882 Target 2 sgRNA" <400> 288 ugaacuuaaa gacucagcuc acagaguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 289 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R1162X nAPG09882 Target 3 sgRNA" <400> 289 uuaaagacuc agcucacaga ucgcaguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 290 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R1162X nAPG09882 Target 4 sgRNA" <400> 290 uaaagacuca gcucacagau cgcauguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 291 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R1162X nAPG09882 Target 5 sgRNA" <400> 291 aaagacucag cucacagauc gcaucguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 292 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R1162X nAPG06646 Target 1 sgRNA" <400> 292 caaugaacuu aaagacucag cucacgccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 293 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R1162X nAPG06646 Target 2 sgRNA" <400> 293 augaacuuaa agacucagcu cacaggccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 294 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R1162X nAPG06646 Target 3 sgRNA" <400> 294 aacuuaaaga cucagcucac agaucgccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 295 <211> 163 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R1162X nAPG03850 Target 1 sgRNA" <400> 295 augaacuuaa agacucagcu gcuauaguuc cauaagaaaa aaguuucuua aguuacuaua 60 guaagggcaa ugacccgugg cguuugggga ucgccuuauc cugguaugga uauucuccccc 120 augugaaaag caccuaagca uagcgcuaug gugcuuuuau uuu 163 <210> 296 <211> 163 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R1162X nAPG03850 Target 2 sgRNA" <400> 296 acuuaaagac ucagcucaca gcuauaguuc cauaagaaaa aaguuucuua aguuacuaua 60 guaagggcaa ugacccgugg cguuugggga ucgccuuauc cugguaugga uauucuccccc 120 augugaaaag caccuaagca uagcgcuaug gugcuuuuau uuu 163 <210> 297 <211> 163 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R1162X nAPG03850 Target 3 sgRNA" <400> 297 agacucagcu cacagaucgc gcuauaguuc cauaagaaaa aaguuucuua aguuacuaua 60 guaagggcaa ugacccgugg cguuugggga ucgccuuauc cugguaugga uauucuccccc 120 augugaaaag caccuaagca uagcgcuaug gugcuuuuau uuu 163 <210> 298 <211> 110 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R1162X nAPG05586 Target 1 sgRNA" <400> 298 aaugaacuua aagacucagc guuauuguac ucucacaauaaa aaguuauuga gaaucuacaa 60 uaauaaggca ucuugccgaa uuuaccgccc uacauaugua gggcgguuuu 110 <210> 299 <211> 110 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R1162X nAPG05586 Target 2 sgRNA" <400> 299 uuaaagacuc agcucacaga guuauuguac ucucauaaa aaguuauuga gaaucuacaa 60 uaauaaggca ucuugccgaa uuuaccgccc uacauaugua gggcgguuuu 110 <210> 300 <211> 110 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R1162X nAPG05586 Target 3 sgRNA" <400> 300 cagcucacag aucgcaucug guuauuguac ucucacaauaaa aaguuauuga gaaucuacaa 60 uaauaaggca ucuugccgaa uuuaccgccc uacauaugua gggcgguuuu 110 <210> 301 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R1162X nAPG00969 Target 1 sgRNA" <400> 301 gucaaugaac uuaaagacuc agcucguuuu aguacucugu gaaagcacag aaucuacuaa 60 118 <210> 302 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R1162X nAPG00969 Target 2 sgRNA" <400> 302 aaagacucag cucacagauc gcaucguuuu aguacucugu gaaagcacag aaucuacuaa 60 118 <210> 303 <211> 151 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R1162X nAPG07553 Target 1 sgRNA" <400> 303 agacucagcu cacagaucgc gcuauaguuc cauaagaaag cuuaaguuac uauaguaagg 60 gcaaugaccc guggcguuug gggaucgccu cauccauuac ggauauucuc cccaugugaa 120 aagcaccuaa gcauaaggcu aaggugcuuu u 151 <210> 304 <211> 105 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF R1162X nAPG01604 Target 1 sgRNA" <400> 304 acucagcuca cagaucgcau guuuuaguac ucuguaaaaa guuacagaau cuacuaaaac 60 aaggcaaaau gccguguuua ucucgucaac uuguuggcga gauuu 105 <210> 305 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG09882 Target 1" <400> 305 gtgtgtcttg ggattcaata actttgcaac agtgaaggaa agcctttgga gtgataccac 60 aggtg 65 <210> 306 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG09882 Target 2" <400> 306 gtcttgggat tcaataactt tgcaacagtg aaggaaagcc tttggagtga taccacaggt 60 gagca 65 <210> 307 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG09882 Target 3" <400> 307 cttgggattc aataactttg caacagtgaa ggaaagcctt tggagtgata ccacaggtga 60 gcaaa 65 <210> 308 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG09882 Target 4" <400> 308 gggattcaat aactttgcaa cagtgaagga aagcctttgg agtgatacca caggtgagca 60 65 <210> 309 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG09882 Target 5" <400> 309 gattcaataa ctttgcaaca gtgaaggaaa gcctttggag tgataccaca ggtgagcaaa 60 aggac 65 <210> 310 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG06646 Target 1" <400> 310 tcgatggtgt gtcttgggat tcaataactt tgcaacagtg aaggaaagcc tttggagtga 60 tacca 65 <210> 311 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG06646 Target 2" <400> 311 ttgggattca ataactttgc aacagtgaag gaaagccttt ggaggtgatac cacaggtgag 60 caaaa 65 <210> 312 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG06646 Target 3" <400> 312 tgggattcaa taactttgca acagtgaagg aaagcctttg gagtgatacc acaggtgagc 60 65 <210> 313 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG06646 Target 4" <400> 313 ggattcaata actttgcaac agtgaaggaa agcctttgga gtgataccac aggtgagcaa 60 aagga 65 <210> 314 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG03850 Target 1" <400> 314 tgtcttggga ttcaataact ttgcaacagt gaaggaaagc ctttggagtg ataccacagg 60 <210> 315 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG03850 Target 2" <400> 315 gtcttgggat tcaataactt tgcaacagtg aaggaaagcc tttggagtga taccacaggt 60 <210> 316 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG03850 Target 3" <400> 316 cttgggattc aataactttg caacagtgaa ggaaagcctt tggagtgata ccacaggtga 60 <210> 317 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG03850 Target 4" <400> 317 tgggattcaa taactttgca acagtgaagg aaagcctttg gagtgatacc acaggtgagc 60 <210> 318 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG07553 Target 1" <400> 318 cttgggattc aataactttg caacagtgaa ggaaagcctt tggagtgata ccacaggtga 60 <210> 319 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG07553 Target 2" <400> 319 tgggattcaa taactttgca acagtgaagg aaagcctttg gagtgatacc acaggtgagc 60 <210> 320 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG01604 Target 1" <400> 320 tcttgggatt caataacttt gcaacagtga aggaaagcct ttggagtgat accacaggtg 60 <210> 321 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG01604 Target 2" <400> 321 cttgggattc aataactttg caacagtgaa ggaaagcctt tggagtgata ccacaggtga 60 <210> 322 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG07433.1 Target 1" <400> 322 ttgggattca ataactttgc aacagtgaag gaaagccttt ggaggtgatac cacaggtgag 60 caaaa 65 <210> 323 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG09748 Target 1" <400> 323 gtatcactcc aaaggctttc cttcactgtt gcaaagttat tgaatcccaa gacacaccat 60 <210> 324 <211> 60 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG05586 Target 1" <400> 324 gattcaataa ctttgcaaca gtgaaggaaa gcctttggag tgataccaca ggtgagcaaa 60 <210> 325 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG09882 Target 1" <400> 325 actttgcaac agtgaaggaa agcct 25 <210> 326 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG09882 Target 2" <400> 326 tgcaacagtg aaggaaagcc tttgg 25 <210> 327 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG09882 Target 3" <400> 327 caacagtgaa ggaaagcctt tggag 25 <210> 328 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG09882 Target 4" <400> 328 cagtgaagga aagcctttgg agtga 25 <210> 329 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG09882 Target 5" <400> 329 gtgaaggaaa gcctttggag tgata 25 <210> 330 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG06646 Target 1" <400> 330 tcaataactt tgcaacagtg aagga 25 <210> 331 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG06646 Target 2" <400> 331 aacagtgaag gaaagccttt ggagt 25 <210> 332 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG06646 Target 3" <400> 332 acagtgaagg aaagcctttg gaggg 25 <210> 333 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG06646 Target 4" <400> 333 agtgaaggaa agcctttgga gtgat 25 <210> 334 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG03850 Target 1" <400> 334 ttgcaacagt gaaggaaagc 20 <210> 335 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG03850 Target 2" <400> 335 tgcaacagtg aaggaaagcc 20 <210> 336 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG03850 Target 3" <400> 336 caacagtgaa ggaaagcctt 20 <210> 337 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG03850 Target 4" <400> 337 acagtgaagg aaagcctttg 20 <210> 338 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG07553 Target 1" <400> 338 caacagtgaa ggaaagcctt 20 <210> 339 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG07553 Target 2" <400> 339 acagtgaagg aaagcctttg 20 <210> 340 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG01604 Target 1" <400> 340 gcaacagtga aggaaagcct 20 <210> 341 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG01604 Target 2" <400> 341 caacagtgaa ggaaagcctt 20 <210> 342 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG07433.1 Target 1" <400> 342 aacagtgaag gaaagccttt ggagt 25 <210> 343 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG09748 Target 1" <400> 343 cttcactgtt gcaaagttat 20 <210> 344 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="CF W1282X nAPG05586 Target 1" <400> 344 gtgaaggaaa gcctttggag 20 <210> 345 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF W1282X nAPG09882 Target 1 sgRNA" <400> 345 acuuugcaac agugaaggaa agccuguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 346 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF W1282X nAPG09882 Target 2 sgRNA" <400> 346 ugcaacagug aaggaaagcc uuuggguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 347 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF W1282X nAPG09882 Target 3 sgRNA" <400> 347 caacagugaa ggaaagccuu uggagguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 348 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF W1282X nAPG09882 Target 4 sgRNA" <400> 348 cagugaagga aagccuuugg agugaguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 349 <211> 118 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF W1282X nAPG09882 Target 5 sgRNA" <400> 349 gugaaggaaa gccuuuggag ugauaguuuu uguacucuca auaaaaaguu auugagaauc 60 uacaaaaaua aggcauuuug ccgaauuuac cgcccuacau auguagggcg guuuuuuu 118 <210> 350 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF W1282X nAPG06646 Target 1 sgRNA" <400> 350 ucauaacuu ugcaacagug aaggagccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 351 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF W1282X nAPG06646 Target 2 sgRNA" <400> 351 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 352 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF W1282X nAPG06646 Target 3 sgRNA" <400> 352 acagugaagg aaagccuuug gaguggccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 353 <211> 164 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF W1282X nAPG06646 Target 4 sgRNA" <400> 353 agugaaggaa agccuuugga gugaugccau aauuccucug uaaaacuuaa agaagguuua 60 uagaguuauu augguaaggc aauaugccgu ggcguuggggg aucgccuaug uccgguuuua 120 164 <210> 354 <211> 163 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF W1282X nAPG03850 Target 1 sgRNA" <400> 354 uugcaacagu gaaggaaagc gcuauaguuc cauaagaaaa aaguuucuua aguuacuaua 60 guaagggcaa ugacccgugg cguuugggga ucgccuuauc cugguaugga uauucuccccc 120 augugaaaag caccuaagca uagcgcuaug gugcuuuuau uuu 163 <210> 355 <211> 163 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF W1282X nAPG03850 Target 2 sgRNA" <400> 355 ugcaacagug aaggaaagcc gcuauaguuc cauaagaaaa aaguuucuua aguuacuaua 60 guaagggcaa ugacccgugg cguuugggga ucgccuuauc cugguaugga uauucuccccc 120 augugaaaag caccuaagca uagcgcuaug gugcuuuuau uuu 163 <210> 356 <211> 163 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF W1282X nAPG03850 Target 3 sgRNA" <400> 356 caacagugaa ggaaagccuu gcuauaguuc cauaagaaaa aaguuucuua aguuacuaua 60 guaagggcaa ugacccgugg cguuugggga ucgccuuauc cugguaugga uauucuccccc 120 augugaaaag caccuaagca uagcgcuaug gugcuuuuau uuu 163 <210> 357 <211> 163 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF W1282X nAPG03850 Target 4 sgRNA" <400> 357 acagugaagg aaagccuuug gcuauaguuc cauaagaaaa aaguuucuua aguuacuaua 60 guaagggcaa ugacccgugg cguuugggga ucgccuuauc cugguaugga uauucuccccc 120 augugaaaag caccuaagca uagcgcuaug gugcuuuuau uuu 163 <210> 358 <211> 151 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF W1282X nAPG07553 Target 1 sgRNA" <400> 358 caacagugaa ggaaagccuu gcuauaguuc cauaagaaag cuuaaguuac uauaguaagg 60 gcaaugaccc guggcguuug gggaucgccu cauccauuac ggauauucuc cccaugugaa 120 aagcaccuaa gcauaaggcu aaggugcuuu u 151 <210> 359 <211> 151 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF W1282X nAPG07553 Target 2 sgRNA" <400> 359 acagugaagg aaagccuuug gcuauaguuc cauaagaaag cuuaaguuac uauaguaagg 60 gcaaugaccc guggcguuug gggaucgccu cauccauuac ggauauucuc cccaugugaa 120 aagcaccuaa gcauaaggcu aaggugcuuu u 151 <210> 360 <211> 105 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF W1282X nAPG01604 Target 1 sgRNA" <400> 360 gcaacaguga aggaaagccu guuuuaguac ucuguaaaaa guuacagaau cuacuaaaac 60 aaggcaaaau gccguguuua ucucgucaac uuguuggcga gauuu 105 <210> 361 <211> 105 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF W1282X nAPG01604 Target 2 sgRNA" <400> 361 caacagugaa ggaaagccuu guuuuaguac ucuguaaaaa guuacagaau cuacuaaaac 60 aaggcaaaau gccguguuua ucucgucaac uuguuggcga gauuu 105 <210> 362 <211> 135 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF W1282X nAPG07433.1 Target 1 sgRNA" <400> 362 aacagugaag gaaagccuuu ggagugucau aguuccauua aagccaaaag uggcuuugau 60 120 uucuccccau uuauu 135 <210> 363 <211> 135 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF W1282X nAPG09748 Target 1 sgRNA" <400> 363 cgacgguuag aggccguaug ucgauuugcu uuaauuucgu gcgugugcau ugucguccuc 60 cauuacaggg cggcuaccac gaauagccac gaaguaaaag cuucguggcu agcaccuuca 120 cuguugcaaa guuau 135 <210> 364 <211> 110 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="CF W1282X nAPG05586 Target 1 sgRNA" <400> 364 gugaaggaaa gccuuuggag guuauuguac ucucacaauaaa aaguuauuga gaaucuacaa 60 uaauaaggca ucuugccgaa uuuaccgccc uacauaugua gggcgguuuu 110 <210> 365 <211> 8 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic peptide" <220> <221> source <223> /note="APG07433.1 deleted motif" <400> 365 Leu Lys Lys Glu Arg Asn Gly Ala 1 5 <210> 366 <211> 1063 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="APG07433.1 engineered deletion" <400> 366 Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu Asp Ile Gly Thr Asn Ser 1 5 10 15 Ile Gly Trp Gly Val Ile Glu Leu Ser Trp Asn Lys Asp Arg Glu Arg 20 25 30 Tyr Glu Lys Val Arg Ile Val Asp Gln Gly Val Arg Met Phe Asp Arg 35 40 45 Ala Glu Met Pro Lys Thr Gly Ala Ser Leu Ala Glu Pro Arg Arg Ile 50 55 60 Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys Ser Gln Arg Lys Lys 65 70 75 80 Asn Ile Arg Asn Leu Leu Val Gln His Gly Val Ile Thr Gln Glu Glu 85 90 95 Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys Ser Met Asp Ile Trp Gly 100 105 110 Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn His Phe Glu Trp Ala 115 120 125 Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly Phe Lys Ser Asn Arg 130 135 140 Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly Lys Val Leu Ser Ser Ile 145 150 155 160 Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr Arg Thr Val Gly Glu Met 165 170 175 Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr Asp Arg Lys Arg Asn Ser 180 185 190 Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala Glu Leu Glu Lys Glu 195 200 205 Ile Val Thr Leu Phe Ala Ala Gln Arg Arg Phe Gln Ser Pro Tyr Ala 210 215 220 Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln Ile Trp Thr His Gln Leu 225 230 235 240 Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys Val Gly Tyr Cys Ser 245 250 255 Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys Ala Thr Tyr Thr Phe 260 265 270 Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg Thr Arg Leu Gly Pro 275 280 285 Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg Glu Ile Ile Leu Asn Asn 290 295 300 Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys Thr Ile Pro Glu Val 305 310 315 320 Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu Asp Glu Thr Ile Gln 325 330 335 Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu Leu Lys Lys Ile Glu 340 345 350 Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr Glu Ile Asn Lys Val 355 360 365 Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu Thr Phe Ser Thr Leu Asp 370 375 380 Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val Tyr Lys Thr Asp Lys Asp 385 390 395 400 Ile Arg Ser Tyr Leu Lys Ser Ser His Asn Leu Pro Lys Arg Cys Tyr 405 410 415 Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser Leu Ser Tyr Thr Lys Phe 420 425 430 Gly His Leu Ser Leu Lys Ala Ile Asn His Val Leu Ser Ile Met Gln 435 440 445 Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp Gln Leu Gly Tyr Asp Thr 450 455 460 Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys Phe Leu Pro Pro Ile Ser 465 470 475 480 Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala Leu Thr Gln Ala Arg 485 490 495 Lys Val Val Asn Ala Ile Ile Arg Arg His Gly Ser Pro His Ser Val 500 505 510 His Ile Glu Leu Ala Arg Glu Leu Ser Lys Asn His Asp Glu Arg Thr 515 520 525 Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr Lys Lys Asn Lys Gly Ala 530 535 540 Ile Ser Ile Leu Ser Glu His Gly Ile Leu Asn Pro Thr Gly Tyr Asp 545 550 555 560 Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly Glu Arg Cys Ala Tyr 565 570 575 Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe Phe Asn Glu Pro Ile Leu 580 585 590 Glu Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr 595 600 605 His Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn 610 615 620 Arg Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala 625 630 635 640 Phe Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg 645 650 655 Glu Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile 660 665 670 Lys Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys 675 680 685 Asn Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro 690 695 700 Arg Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe 705 710 715 720 Arg Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His 725 730 735 His Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val 740 745 750 Thr Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val 755 760 765 Lys Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu 770 775 780 Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu 785 790 795 800 Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser Arg Met 805 810 815 Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr Ile Met Arg 820 825 830 Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile Glu Arg Leu 835 840 845 His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp Phe Lys Met Val 850 855 860 Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu Ala Ile Lys Gln Arg Tyr 865 870 875 880 Leu Glu His Gly Lys Asn Ser Lys Lys Ala Phe Glu Thr Pro Leu Tyr 885 890 895 Lys Pro Ser Lys Lys Gly Thr Gly Asn Leu Ile Lys Arg Val Lys Val 900 905 910 Glu Gly Gln Ala Lys Ser Phe Val Arg Glu Val Asn Gly Gly Val Ala 915 920 925 Gln Asn Gly Asp Leu Val Arg Val Asp Leu Phe Glu Lys Asp Asp Lys 930 935 940 Tyr Tyr Met Val Pro Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu 945 950 955 960 Pro Lys Lys Val Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr 965 970 975 Leu Asp Asn Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu 980 985 990 Val Arg Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr 995 1000 1005 Leu Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys 1010 1015 1020 Pro Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu 1025 1030 1035 Asp Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu 1040 1045 1050 Val Arg Lys Glu Thr Arg Arg Asn Phe His 1055 1060 <210> 367 <211> 8 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic peptide" <220> <221> source <223> /note="APG08290.1 deleted motif" <400> 367 Leu Lys Lys Glu Arg Asn Gly Ser 1 5 <210> 368 <211> 1064 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="APG08290.1 engineered deletion" <400> 368 Met Ser Glu Leu Asp Tyr Arg Ile Gly Leu Asp Ile Gly Thr Asn Ser 1 5 10 15 Ile Gly Trp Gly Val Ile Glu Leu Phe Trp Asn Lys Asp Arg Glu Arg 20 25 30 Tyr Glu Lys Val Arg Ile Val Asp Lys Gly Val Arg Met Phe Asp Lys 35 40 45 Ala Glu Ile Pro Asn Lys Gly Ala Ser Leu Ala Glu Pro Arg Arg Ile 50 55 60 Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys Ser Gln Arg Lys Lys 65 70 75 80 Glu Ile Arg Asn Leu Leu Val Gln His Gly Met Ile Thr Gln Glu Glu 85 90 95 Leu Asp Leu Leu Tyr Pro Leu Ser Lys Lys Ser Ile Asp Ile Trp Asp 100 105 110 Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn His Leu Glu Trp Ala 115 120 125 Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly Phe Lys Ser Asn Arg 130 135 140 Lys Ser Glu Leu Lys Asp Ala Glu Thr Gly Lys Val Leu Ser Ser Ile 145 150 155 160 Gln Val Asn Glu Lys Arg Leu Phe Leu Tyr Arg Thr Val Gly Glu Met 165 170 175 Trp Ile Lys Asp Ala Glu Phe Ser Lys Tyr Asp Arg Arg Arg Asn Ser 180 185 190 Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala Asp Leu Glu Lys Glu 195 200 205 Ile Val Thr Leu Phe Glu Ala Gln Arg Lys Phe Gln Ser Ser Tyr Ala 210 215 220 Ser Lys Asn Leu Gln Glu Thr Tyr Leu Gln Ile Trp Ala His Gln Leu 225 230 235 240 Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys Val Gly Tyr Cys Ser 245 250 255 Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys Ala Thr Tyr Thr Phe 260 265 270 Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg Thr Arg Leu Gly Pro 275 280 285 Asp Phe Gln Pro Phe Thr Gln Glu Gln Lys Glu Ile Ile Leu Asp Lys 290 295 300 Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys Thr Ile Pro Glu Val 305 310 315 320 Ser Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu Asp Glu Thr Ile Gln 325 330 335 Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu Leu Lys Lys Ile Glu 340 345 350 Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr Glu Ile Lys Lys Val 355 360 365 Val Ala Asn Tyr Ala Glu Arg Thr Asn Glu Ala Phe Ser Thr Leu Asp 370 375 380 Tyr Asp Ala Ile Ala Tyr Ala Leu Thr Val Tyr Lys Thr Asp Lys Asp 385 390 395 400 Ile Arg Ser Tyr Leu Lys Lys Ser Asn Asn Leu Ser Lys Arg Cys Tyr 405 410 415 Asp Asp Gln Leu Ile Glu Glu Leu Phe Thr Leu Ser Tyr Thr Lys Phe 420 425 430 Gly His Leu Ser Phe Lys Ala Ile Asn His Val Leu Pro Ile Met Gln 435 440 445 Glu Gly Arg Thr Tyr Gln Glu Ala Ile His Gln Leu Gly Tyr Asp Thr 450 455 460 Thr Asn Leu Lys Lys Glu Asn Arg Ser Met Phe Leu Pro Leu Ile Pro 465 470 475 480 Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala Ile Thr Gln Ala Arg 485 490 495 Lys Val Val Asn Ala Ile Ile Arg Arg Tyr Gly Ser Pro Asn Ser Val 500 505 510 His Ile Glu Leu Ala Arg Glu Leu Ser Lys Ser His Asp Glu Arg Lys 515 520 525 Lys Ile Met Thr Ala His Asp Glu Asn Tyr Lys Lys Asn Lys Gly Ala 530 535 540 Ile Ser Ile Leu Ile Glu Asn Gly Ile Leu Asn Pro Thr Gly Tyr Asp 545 550 555 560 Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly Glu Arg Cys Ala Tyr 565 570 575 Ser Leu Lys Glu Ile Pro Pro Asp Thr Phe Phe Asn Glu Pro Ile Leu 580 585 590 Glu Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr 595 600 605 His Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Asn Lys Gly Asn 610 615 620 Arg Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala 625 630 635 640 Phe Glu Arg Tyr Val Arg Ser Asn Lys Leu Phe Ser Lys Lys Lys Arg 645 650 655 Glu Tyr Leu Leu Lys Lys Thr Tyr Leu Pro Arg Glu Ser Glu Leu Ile 660 665 670 Lys Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys 675 680 685 Asn Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Val Glu Val Asn Leu 690 695 700 Arg Lys Lys Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Leu 705 710 715 720 Arg Lys Arg Trp Gly Leu Glu Lys Asn Arg Gln Glu Thr Tyr Leu His 725 730 735 His Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val 740 745 750 Thr Arg Ile Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val 755 760 765 Lys Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu 770 775 780 Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu 785 790 795 800 Leu Lys Ala Gly Tyr Gln Ser Ser Asp Tyr Ile Phe Val Ser Arg Met 805 810 815 Pro Lys Arg Ser Val Thr Gly Ala Ala His Asp Gln Thr Ile Arg Arg 820 825 830 Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile Lys Arg Val 835 840 845 Arg Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp Phe Lys Met Val 850 855 860 Gly Lys Glu Gln Asp Leu Ala Thr Tyr Glu Ala Ile Lys Gln Arg Tyr 865 870 875 880 Leu Glu His Arg Lys Asn Ser Lys Lys Ala Phe Glu Thr Pro Leu Tyr 885 890 895 Lys Pro Ser Lys Lys Gly Thr Gly Asn Leu Ile Lys Arg Val Lys Ile 900 905 910 Glu Gly Gln Thr Lys Ala Phe Val Arg Glu Val Asn Gly Gly Val Ala 915 920 925 Gln Asn Ser Asp Leu Val Arg Val Asp Leu Phe Glu Lys Asp Asp Lys 930 935 940 Tyr Tyr Met Val Pro Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu 945 950 955 960 Pro Lys Lys Val Val Lys Ser Gly Lys Gly Tyr Glu Gln Trp Leu Thr 965 970 975 Leu Asp Asn Ser Phe Thr Phe Lys Ser Ser Leu Tyr Pro Tyr Asp Leu 980 985 990 Val Arg Leu Val Lys Gly Asn Glu Asp Arg Phe Leu Tyr Phe Gly Thr 995 1000 1005 Leu Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys 1010 1015 1020 Pro Ser Lys Gln Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu 1025 1030 1035 Asn Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu 1040 1045 1050 Val Lys Gln Glu Thr Arg Arg Ile Phe Asn Arg 1055 1060 <210> 369 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000139 target sequence" <400> 369 aggttttaat ggcccagcct 20 <210> 370 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000143 target sequence" <400> 370 catggcagta cattagagca 20 <210> 371 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000169 target sequence" <400> 371 cacatctcga gcaagacgtt 20 <210> 372 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000173 target sequence" <400> 372 cttctatagc ctccttcccc 20 <210> 373 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000186 target sequence" <400> 373 ggacagtgcg catctccctg 20 <210> 374 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000194 target sequence" <400> 374 gccgcacagc attcaggtcg 20 <210> 375 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000926 target sequence" <400> 375 agagccatca ccatcacatc cctaa 25 <210> 376 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000927 target sequence" <400> 376 ggccaaaatc cagctgcctt ccttg 25 <210> 377 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000928 target sequence" <400> 377 gcttctactc ttggcttaca accca 25 <210> 378 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000929 target sequence" <400> 378 atctggaggg aacttacagc atatg 25 <210> 379 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000930 target sequence" <400> 379 gaacaactca aatggaaatg aatat 25 <210> 380 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000931 target sequence" <400> 380 tcctgttcca tcaccatcaa aaaaa 25 <210> 381 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000935 target sequence" <400> 381 tgttggttac ctccctgcca ccacc 25 <210> 382 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN001101 target sequence" <400> 382 atattttctt taatggtgcc aggca 25 <210> 383 <211> 130 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000139 sgRNA" <400> 383 agguuuuaau ggcccagccu gucauaguuc cauuaaagcc aaaaguggcu uugauguuuc 60 uaugauaagg guuucgaccc guggcgucgg ggaucgccug cccauugaaa ugggcuucuc 120 cccauuuauu 130 <210> 384 <211> 130 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000143 sgRNA" <400> 384 cauggcagua cauuagagca gucauaguuc cauuaaagcc aaaaguggcu uugauguuuc 60 uaugauaagg guuucgaccc guggcgucgg ggaucgccug cccauugaaa ugggcuucuc 120 cccauuuauu 130 <210> 385 <211> 130 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000169 sgRNA" <400> 385 cacaucga gcaagacguu gucauaguuc cauuaaagcc aaaaguggcu uugauguuuc 60 uaugauaagg guuucgaccc guggcgucgg ggaucgccug cccauugaaa ugggcuucuc 120 cccauuuauu 130 <210> 386 <211> 130 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000173 sgRNA" <400> 386 cuucuauagc cuccuuccccc gucauaguuc cauuaaagcc aaaaguggcu uugauguuuc 60 uaugauaagg guuucgaccc guggcgucgg ggaucgccug cccauugaaa ugggcuucuc 120 cccauuuauu 130 <210> 387 <211> 130 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000186 sgRNA" <400> 387 ggacagugcg caucucccug gucauaguuc cauuaaagcc aaaaguggcu uugauguuuc 60 uaugauaagg guuucgaccc guggcgucgg ggaucgccug cccauugaaa ugggcuucuc 120 cccauuuauu 130 <210> 388 <211> 130 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000194 sgRNA" <400> 388 gccgcacagc auucaggucg gucauaguuc cauuaaagcc aaaaguggcu uugauguuuc 60 uaugauaagg guuucgaccc guggcgucgg ggaucgccug cccauugaaa ugggcuucuc 120 cccauuuauu 130 <210> 389 <211> 135 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000926 sgRNA" <400> 389 agagccauca ccaucacauc ccuaagucau aguuccauga aagccaaaag uggcuuugau 60 guuucuauga uaaggguuuc ggcccguggc gucggggauc gccugcccau uccgaugggc 120 uucuccccau uuauu 135 <210> 390 <211> 135 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000927 sgRNA" <400> 390 ggccaaaauc cagcugccuu ccuuggucau aguuccauga aagccaaaag uggcuuugau 60 guuucuauga uaaggguuuc ggcccguggc gucggggauc gccugcccau uccgaugggc 120 uucuccccau uuauu 135 <210> 391 <211> 135 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000928 sgRNA" <400> 391 gcuucuacuc uuggcuuaca acccagucau aguuccauga aagccaaaag uggcuuugau 60 guuucuauga uaaggguuuc ggcccguggc gucggggauc gccugcccau uccgaugggc 120 uucuccccau uuauu 135 <210> 392 <211> 135 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000929 sgRNA" <400> 392 auuggaggg aacuuacagc auauggucau aguuccauga aagccaaaag uggcuuugau 60 guuucuauga uaaggguuuc ggcccguggc gucggggauc gccugcccau uccgaugggc 120 uucuccccau uuauu 135 <210> 393 <211> 135 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000930 sgRNA" <400> 393 gaacaacuca aauggaaaug aauaugucau aguuccauga aagccaaaag uggcuuugau 60 guuucuauga uaaggguuuc ggcccguggc gucggggauc gccugcccau uccgaugggc 120 uucuccccau uuauu 135 <210> 394 <211> 135 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000931 sgRNA" <400> 394 uccuguucca ucaccaucaa aaaaagucau aguuccauga aagccaaaag uggcuuugau 60 guuucuauga uaaggguuuc ggcccguggc gucggggauc gccugcccau uccgaugggc 120 uucuccccau uuauu 135 <210> 395 <211> 135 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000935 sgRNA" <400> 395 uguugguuac cucccugcca ccaccgucau aguuccauga aagccaaaag uggcuuugau 60 guuucuauga uaaggguuuc ggcccguggc gucggggauc gccugcccau uccgaugggc 120 uucuccccau uuauu 135 <210> 396 <211> 130 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN001101 sgRNA" <400> 396 auauuuucuu uaauggugcc aggcagucau aguuccauua aagccaaaag uggcuuugau 60 120 uuccccccau 130 <210> 397 <211> 1063 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="nAPG07433.1-del" <400> 397 Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu Ala Ile Gly Thr Asn Ser 1 5 10 15 Ile Gly Trp Gly Val Ile Glu Leu Ser Trp Asn Lys Asp Arg Glu Arg 20 25 30 Tyr Glu Lys Val Arg Ile Val Asp Gln Gly Val Arg Met Phe Asp Arg 35 40 45 Ala Glu Met Pro Lys Thr Gly Ala Ser Leu Ala Glu Pro Arg Arg Ile 50 55 60 Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys Ser Gln Arg Lys Lys 65 70 75 80 Asn Ile Arg Asn Leu Leu Val Gln His Gly Val Ile Thr Gln Glu Glu 85 90 95 Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys Ser Met Asp Ile Trp Gly 100 105 110 Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn His Phe Glu Trp Ala 115 120 125 Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly Phe Lys Ser Asn Arg 130 135 140 Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly Lys Val Leu Ser Ser Ile 145 150 155 160 Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr Arg Thr Val Gly Glu Met 165 170 175 Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr Asp Arg Lys Arg Asn Ser 180 185 190 Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala Glu Leu Glu Lys Glu 195 200 205 Ile Val Thr Leu Phe Ala Ala Gln Arg Arg Phe Gln Ser Pro Tyr Ala 210 215 220 Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln Ile Trp Thr His Gln Leu 225 230 235 240 Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys Val Gly Tyr Cys Ser 245 250 255 Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys Ala Thr Tyr Thr Phe 260 265 270 Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg Thr Arg Leu Gly Pro 275 280 285 Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg Glu Ile Ile Leu Asn Asn 290 295 300 Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys Thr Ile Pro Glu Val 305 310 315 320 Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu Asp Glu Thr Ile Gln 325 330 335 Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu Leu Lys Lys Ile Glu 340 345 350 Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr Glu Ile Asn Lys Val 355 360 365 Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu Thr Phe Ser Thr Leu Asp 370 375 380 Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val Tyr Lys Thr Asp Lys Asp 385 390 395 400 Ile Arg Ser Tyr Leu Lys Ser Ser His Asn Leu Pro Lys Arg Cys Tyr 405 410 415 Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser Leu Ser Tyr Thr Lys Phe 420 425 430 Gly His Leu Ser Leu Lys Ala Ile Asn His Val Leu Ser Ile Met Gln 435 440 445 Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp Gln Leu Gly Tyr Asp Thr 450 455 460 Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys Phe Leu Pro Pro Ile Ser 465 470 475 480 Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala Leu Thr Gln Ala Arg 485 490 495 Lys Val Val Asn Ala Ile Ile Arg Arg His Gly Ser Pro His Ser Val 500 505 510 His Ile Glu Leu Ala Arg Glu Leu Ser Lys Asn His Asp Glu Arg Thr 515 520 525 Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr Lys Lys Asn Lys Gly Ala 530 535 540 Ile Ser Ile Leu Ser Glu His Gly Ile Leu Asn Pro Thr Gly Tyr Asp 545 550 555 560 Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly Glu Arg Cys Ala Tyr 565 570 575 Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe Phe Asn Glu Pro Ile Leu 580 585 590 Glu Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr 595 600 605 His Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn 610 615 620 Arg Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala 625 630 635 640 Phe Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg 645 650 655 Glu Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile 660 665 670 Lys Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys 675 680 685 Asn Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro 690 695 700 Arg Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe 705 710 715 720 Arg Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His 725 730 735 His Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val 740 745 750 Thr Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val 755 760 765 Lys Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu 770 775 780 Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu 785 790 795 800 Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser Arg Met 805 810 815 Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr Ile Met Arg 820 825 830 Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile Glu Arg Leu 835 840 845 His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp Phe Lys Met Val 850 855 860 Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu Ala Ile Lys Gln Arg Tyr 865 870 875 880 Leu Glu His Gly Lys Asn Ser Lys Lys Ala Phe Glu Thr Pro Leu Tyr 885 890 895 Lys Pro Ser Lys Lys Gly Thr Gly Asn Leu Ile Lys Arg Val Lys Val 900 905 910 Glu Gly Gln Ala Lys Ser Phe Val Arg Glu Val Asn Gly Gly Val Ala 915 920 925 Gln Asn Gly Asp Leu Val Arg Val Asp Leu Phe Glu Lys Asp Asp Lys 930 935 940 Tyr Tyr Met Val Pro Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu 945 950 955 960 Pro Lys Lys Val Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr 965 970 975 Leu Asp Asn Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu 980 985 990 Val Arg Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr 995 1000 1005 Leu Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys 1010 1015 1020 Pro Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu 1025 1030 1035 Asp Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu 1040 1045 1050 Val Arg Lys Glu Thr Arg Arg Asn Phe His 1055 1060 <210> 398 <211> 1064 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="nAPG08290.1-del" <400> 398 Met Ser Glu Leu Asp Tyr Arg Ile Gly Leu Ala Ile Gly Thr Asn Ser 1 5 10 15 Ile Gly Trp Gly Val Ile Glu Leu Phe Trp Asn Lys Asp Arg Glu Arg 20 25 30 Tyr Glu Lys Val Arg Ile Val Asp Lys Gly Val Arg Met Phe Asp Lys 35 40 45 Ala Glu Ile Pro Asn Lys Gly Ala Ser Leu Ala Glu Pro Arg Arg Ile 50 55 60 Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys Ser Gln Arg Lys Lys 65 70 75 80 Glu Ile Arg Asn Leu Leu Val Gln His Gly Met Ile Thr Gln Glu Glu 85 90 95 Leu Asp Leu Leu Tyr Pro Leu Ser Lys Lys Ser Ile Asp Ile Trp Asp 100 105 110 Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn His Leu Glu Trp Ala 115 120 125 Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly Phe Lys Ser Asn Arg 130 135 140 Lys Ser Glu Leu Lys Asp Ala Glu Thr Gly Lys Val Leu Ser Ser Ile 145 150 155 160 Gln Val Asn Glu Lys Arg Leu Phe Leu Tyr Arg Thr Val Gly Glu Met 165 170 175 Trp Ile Lys Asp Ala Glu Phe Ser Lys Tyr Asp Arg Arg Arg Asn Ser 180 185 190 Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala Asp Leu Glu Lys Glu 195 200 205 Ile Val Thr Leu Phe Glu Ala Gln Arg Lys Phe Gln Ser Ser Tyr Ala 210 215 220 Ser Lys Asn Leu Gln Glu Thr Tyr Leu Gln Ile Trp Ala His Gln Leu 225 230 235 240 Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys Val Gly Tyr Cys Ser 245 250 255 Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys Ala Thr Tyr Thr Phe 260 265 270 Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg Thr Arg Leu Gly Pro 275 280 285 Asp Phe Gln Pro Phe Thr Gln Glu Gln Lys Glu Ile Ile Leu Asp Lys 290 295 300 Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys Thr Ile Pro Glu Val 305 310 315 320 Ser Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu Asp Glu Thr Ile Gln 325 330 335 Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu Leu Lys Lys Ile Glu 340 345 350 Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr Glu Ile Lys Lys Val 355 360 365 Val Ala Asn Tyr Ala Glu Arg Thr Asn Glu Ala Phe Ser Thr Leu Asp 370 375 380 Tyr Asp Ala Ile Ala Tyr Ala Leu Thr Val Tyr Lys Thr Asp Lys Asp 385 390 395 400 Ile Arg Ser Tyr Leu Lys Lys Ser Asn Asn Leu Ser Lys Arg Cys Tyr 405 410 415 Asp Asp Gln Leu Ile Glu Glu Leu Phe Thr Leu Ser Tyr Thr Lys Phe 420 425 430 Gly His Leu Ser Phe Lys Ala Ile Asn His Val Leu Pro Ile Met Gln 435 440 445 Glu Gly Arg Thr Tyr Gln Glu Ala Ile His Gln Leu Gly Tyr Asp Thr 450 455 460 Thr Asn Leu Lys Lys Glu Asn Arg Ser Met Phe Leu Pro Leu Ile Pro 465 470 475 480 Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala Ile Thr Gln Ala Arg 485 490 495 Lys Val Val Asn Ala Ile Ile Arg Arg Tyr Gly Ser Pro Asn Ser Val 500 505 510 His Ile Glu Leu Ala Arg Glu Leu Ser Lys Ser His Asp Glu Arg Lys 515 520 525 Lys Ile Met Thr Ala His Asp Glu Asn Tyr Lys Lys Asn Lys Gly Ala 530 535 540 Ile Ser Ile Leu Ile Glu Asn Gly Ile Leu Asn Pro Thr Gly Tyr Asp 545 550 555 560 Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly Glu Arg Cys Ala Tyr 565 570 575 Ser Leu Lys Glu Ile Pro Pro Asp Thr Phe Phe Asn Glu Pro Ile Leu 580 585 590 Glu Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr 595 600 605 His Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Asn Lys Gly Asn 610 615 620 Arg Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala 625 630 635 640 Phe Glu Arg Tyr Val Arg Ser Asn Lys Leu Phe Ser Lys Lys Lys Arg 645 650 655 Glu Tyr Leu Leu Lys Lys Thr Tyr Leu Pro Arg Glu Ser Glu Leu Ile 660 665 670 Lys Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys 675 680 685 Asn Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Val Glu Val Asn Leu 690 695 700 Arg Lys Lys Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Leu 705 710 715 720 Arg Lys Arg Trp Gly Leu Glu Lys Asn Arg Gln Glu Thr Tyr Leu His 725 730 735 His Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val 740 745 750 Thr Arg Ile Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val 755 760 765 Lys Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu 770 775 780 Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu 785 790 795 800 Leu Lys Ala Gly Tyr Gln Ser Ser Asp Tyr Ile Phe Val Ser Arg Met 805 810 815 Pro Lys Arg Ser Val Thr Gly Ala Ala His Asp Gln Thr Ile Arg Arg 820 825 830 Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile Lys Arg Val 835 840 845 Arg Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp Phe Lys Met Val 850 855 860 Gly Lys Glu Gln Asp Leu Ala Thr Tyr Glu Ala Ile Lys Gln Arg Tyr 865 870 875 880 Leu Glu His Arg Lys Asn Ser Lys Lys Ala Phe Glu Thr Pro Leu Tyr 885 890 895 Lys Pro Ser Lys Lys Gly Thr Gly Asn Leu Ile Lys Arg Val Lys Ile 900 905 910 Glu Gly Gln Thr Lys Ala Phe Val Arg Glu Val Asn Gly Gly Val Ala 915 920 925 Gln Asn Ser Asp Leu Val Arg Val Asp Leu Phe Glu Lys Asp Asp Lys 930 935 940 Tyr Tyr Met Val Pro Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu 945 950 955 960 Pro Lys Lys Val Val Lys Ser Gly Lys Gly Tyr Glu Gln Trp Leu Thr 965 970 975 Leu Asp Asn Ser Phe Thr Phe Lys Ser Ser Leu Tyr Pro Tyr Asp Leu 980 985 990 Val Arg Leu Val Lys Gly Asn Glu Asp Arg Phe Leu Tyr Phe Gly Thr 995 1000 1005 Leu Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys 1010 1015 1020 Pro Ser Lys Gln Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu 1025 1030 1035 Asn Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu 1040 1045 1050 Val Lys Gln Glu Thr Arg Arg Ile Phe Asn Arg 1055 1060 <210> 399 <211> 169 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50140 protein sequence" <400> 399 Met Ser Asp Leu Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Gln Leu Ala Lys Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Thr Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Gln Val Gln Ile Ile Asp Gly Val Leu Ala Pro Glu Cys Ser Gly Leu 130 135 140 Leu Cys Asp Phe Tyr Arg Met Pro Arg Gln Val Phe Asn Gln Gln Lys 145 150 155 160 Ala Glu Ser Thr Ser Ile Asn Gly Asp 165 <210> 400 <211> 164 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50141 protein sequence" <400> 400 Met Ser Asn Pro Glu Leu Thr His Glu His Trp Met Arg Tyr Ala Leu 1 5 10 15 Thr Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Gln Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Ile Glu Phe Thr Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg Gln Pro Arg Gln Val Phe Asn Ala Leu Lys 145 150 155 160 Thr Gly Asn Ala <210> 401 <211> 169 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50142 protein sequence" <400> 401 Met Ser Ile Pro Glu Leu Asn His Asp Val Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Gly Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Gln Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Val Ala Ile Thr Glu Gly Val Leu Arg Glu Glu Cys Ala Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg Gln Pro Arg Gln Val Phe Asn Ala Leu Lys 145 150 155 160 Lys Pro Ala Gly Asp Ile Asn Ala Phe 165 <210> 402 <211> 172 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50143 protein sequence" <400> 402 Met Ser Asn Pro Glu Leu Asn His Glu Tyr Trp Met Arg Tyr Ala Leu 1 5 10 15 Thr Leu Ala Lys Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asp Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Arg Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Leu Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 His Ile Glu Met Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg Gln Pro Arg Gln Val Phe Asn Ala Leu Lys 145 150 155 160 Lys Ser Pro Pro Asp Ile Asn Asn Leu Gln Ala Arg 165 170 <210> 403 <211> 169 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50144 protein sequence" <400> 403 Met Ser Asn Pro Glu Leu Thr His Asp His Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Gln Arg Ala Arg Asn Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Gly Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Val Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Gln Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Val Glu Ile Ile Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg His Pro Arg Gln Val Phe Asn Ala Leu Lys 145 150 155 160 Lys Asn Ala Gly Thr Ile Asn Thr Gln 165 <210> 404 <211> 166 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50145 protein sequence" <400> 404 Met Ser Asp Thr Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Met Leu Ala Lys Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Lys Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Asn Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Val Glu Ile Ala Glu Gly Val Leu Ala Asp Glu Cys Ser Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg His Pro Arg Gln Val Phe Asn Ala Leu Lys 145 150 155 160 Gln Ala Ala Lys His Ile 165 <210> 405 <211> 171 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50146 protein sequence" <400> 405 Met Ser Asp Ile Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Met Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly His Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Ile Glu Phe Thr Glu Gly Val Leu Ala Asp Glu Cys Ser Gly Met 130 135 140 Leu Cys Asp Phe Tyr Arg Tyr Pro Arg Gln Val Phe Asn Thr Leu Lys 145 150 155 160 Gln Ala Ala Lys Ala Ile Asn Pro Ala Ala Gln 165 170 <210> 406 <211> 173 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50147 protein sequence" <400> 406 Met Ser Ile Pro Glu Leu Asn His Asp Val Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Gly Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Gln Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Val Glu Ile Thr Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg Gln Pro Arg Gln Val Phe Asn Ala Leu Lys 145 150 155 160 Lys Pro Ala Gly Asp Ile Asn Ala Leu Gln Asn Asn Arg 165 170 <210> 407 <211> 168 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50148 protein sequence" <400> 407 Met Ser Asn Pro Glu Phe Thr His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Arg Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Thr Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Gln Val Lys Thr Ile Gly Gly Val Leu Ala Pro Glu Cys Ser Gly Leu 130 135 140 Leu Cys Asp Phe Tyr Arg Met Pro Arg Gln Val Phe Asn Gln Gln Lys 145 150 155 160 Ala Glu Leu Lys Ser Ile Asn Asp 165 <210> 408 <211> 167 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50149 protein sequence" <400> 408 Met Ser Asp Ala Glu Leu Thr His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Gln Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Arg Leu Ile Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Val Glu Val Val Glu Gly Ile Leu Arg Asp Glu Cys Ala Gly Met 130 135 140 Leu Cys Asp Phe Tyr Arg Gln Pro Arg Gln Val Phe Asn Ala Leu Lys 145 150 155 160 Lys Gly Ala Thr Asp Ile Asn 165 <210> 409 <211> 167 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50150 protein sequence" <400> 409 Met Ser Asp Ala Glu Leu Thr His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Gln Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Arg Leu Ile Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Val Glu Val Val Glu Gly Ile Leu Arg Asp Glu Cys Ala Gly Met 130 135 140 Leu Cys Ala Phe Tyr Arg Gln Pro Arg Ala Val Lys Asn Ala Leu Lys 145 150 155 160 Lys Gly Ala Thr Asp Val Leu 165 <210> 410 <211> 169 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50151 protein sequence" <400> 410 Met Ser Asp Leu Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Gln Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Tyr Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Thr Leu Val Phe Gly Val Arg Asn Glu Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Met Asn Val Leu Arg Tyr Pro Gly Met Asn His 115 120 125 Gln Val Gln Ile Ile Asp Gly Val Leu Ala Pro Glu Cys Ser Gly Leu 130 135 140 Leu Cys Asp Phe Tyr Arg Met Pro Arg Gln Gln Lys Asn Gln Gln Lys 145 150 155 160 Ala Glu Ser Thr Ser Ser Pro Gly Asp 165 <210> 411 <211> 167 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50152 protein sequence" <400> 411 Met Ser Asp Asn Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Gly Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Thr Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Thr Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Val Glu Ile Val Glu Gly Ile Leu Ser Glu Ser Cys Ala Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg Gln Pro Arg Ala Val Lys Asn Ala Leu Lys 145 150 155 160 Lys Ala Ala Asp Pro Ala Ala 165 <210> 412 <211> 164 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50153 protein sequence" <400> 412 Met Ser Asp Thr Glu Phe Thr His Glu His Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly His Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ile Gly Ser Leu Met Asn Val Leu Gly Tyr Pro Gly Met Asn His 115 120 125 Gln Val Gln Val Ser Glu Gly Val Leu Ala Thr Glu Cys Ser Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg Ala Pro Arg Leu Val Lys Asn Ala Leu Lys 145 150 155 160 Glu Lys Ala Arg <210> 413 <211> 171 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50154 protein sequence" <400> 413 Met Ser Glu Ser Glu Phe Thr His Glu His Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Arg Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Ser Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Gly Arg Ile Gly Asn Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ile Gly Ser Leu Met Asn Val Val Gly Tyr Pro Gly Met Asn His 115 120 125 Gln Ile Asn Val Ile Glu Gly Val Leu Ala Glu Glu Cys Ser Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg Ala Pro Arg Leu Val Lys Asn Ala Leu Lys 145 150 155 160 Glu Lys Ala Arg Asn Gly Asn Asn Pro Asn Lys 165 170 <210> 414 <211> 164 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50155 protein sequence" <400> 414 Met Ser Asn Pro Glu Leu Thr His Glu His Trp Met Arg Tyr Ala Leu 1 5 10 15 Thr Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Gln Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Ile Glu Phe Thr Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg Gln Pro Arg Leu Val Lys Asn Ala Leu Lys 145 150 155 160 Thr Gly Asn Ala <210> 415 <211> 166 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50156 protein sequence" <400> 415 Met Ser Asp Pro Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Gln Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Ile His 85 90 95 Ser Arg Ile Gly Thr Val Val Phe Gly Val Arg Asn Glu Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Leu Asn Val Leu Arg Tyr Pro Gly Met Asn His 115 120 125 Gln Val Asn Val Leu Gly Gly Val Leu Ala Pro Ala Cys Ser Glu Met 130 135 140 Leu Cys Glu Phe Tyr Arg Met Pro Arg Gln Gln Lys Asn Arg Gln Lys 145 150 155 160 Ala Glu Ser Lys Leu Ser 165 <210> 416 <211> 166 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50157 protein sequence" <400> 416 Met Ser Asp Asn Glu Leu Asn His Glu His Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Gln Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Gln Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Met Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Gln Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Val Glu Ile Thr Glu Gly Val Leu Ala Asp Asp Cys Ser Ser Met 130 135 140 Leu Cys Asp Phe Tyr Arg His Pro Arg Glu Gln Lys Asn Ala Leu Lys 145 150 155 160 Arg Ala Ala His Ser Asn 165 <210> 417 <211> 168 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50158 protein sequence" <400> 417 Met Ser Asn Pro Glu His Asn His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Tyr Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Thr Leu Val Phe Gly Val Arg Asn Glu Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Met Asn Val Leu Gly Tyr Pro Gly Met Asn His 115 120 125 Gln Val Gln Thr Ile Gly Gly Val Leu Ala Pro Glu Cys Ser Gly Leu 130 135 140 Leu Cys Asp Phe Tyr Arg Met Pro Arg Gln Gln Lys Asn Gln Gln Lys 145 150 155 160 Ala Glu Leu Asn Gln Pro Gly Asp 165 <210> 418 <211> 168 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50159 protein sequence" <400> 418 Met Ser Asp Leu Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Ser Leu Ala Lys Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Thr Leu Val Tyr Gly Val Arg Asn Glu Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Met Asn Val Leu Gly Tyr Pro Gly Met Asn His 115 120 125 Gln Val Gln Ile Ile Gly Gly Val Leu Ala Pro Asp Cys Ser Gly Leu 130 135 140 Leu Cys Asp Phe Tyr Arg Met Pro Arg Gln Gln Lys Asn Gln Gln Lys 145 150 155 160 Ala Glu Leu Lys Ser Ser Gly Asp 165 <210> 419 <211> 166 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50160 protein sequence" <400> 419 Met Ser Asp His Glu Phe Asn Asp Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Ala Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Ser Arg Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Val Glu Ile Thr Glu Gly Ile Leu Ala Glu Ser Cys Ser Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg Trp Pro Arg Glu Val Lys Asn Ala Leu Lys 145 150 155 160 Lys Ala Arg Gln Glu Glu 165 <210> 420 <211> 166 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50161 protein sequence" <400> 420 Met Ser Gln Thr Glu Leu Thr His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Gly Arg Ile Gly Thr Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Val Gly Ser Leu Met Asn Ile Thr Gly Tyr Pro Gly Met Asn His 115 120 125 Gln Val Gln Val Ile Glu Gly Ile Leu Ala Thr Glu Cys Ser Ala Met 130 135 140 Leu Cys Ala Phe Tyr Arg Gln Pro Arg Leu Val Lys Asn Ala Leu Lys 145 150 155 160 Glu Ala Ala Lys Thr Ala 165 <210> 421 <211> 167 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50162 protein sequence" <400> 421 Met Ser Asn Pro Glu Leu Asn His Asp Tyr Trp Met Arg His Ala Leu 1 5 10 15 Ser Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Arg Asn Asn Glu Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Met Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Gln Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Val Glu Ile Val Glu Gly Val Leu Arg Asp Glu Cys Ala Gly Met 130 135 140 Leu Cys Asp Phe Tyr Arg Gln Pro Arg Leu Val Lys Asn Ala Gln Lys 145 150 155 160 Lys Gly Ala Glu Pro Leu Ile 165 <210> 422 <211> 172 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50163 protein sequence" <400> 422 Met Ser Asn Pro Glu Leu Asn His Glu Tyr Trp Met Arg Tyr Ala Leu 1 5 10 15 Thr Leu Ala Lys Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Tyr Asn Asp Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Arg Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Leu Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 His Ile Glu Met Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg Gln Pro Arg Met Val Lys Asn Ala Leu Lys 145 150 155 160 Lys Ser Pro Pro Asp Ser Pro Asn Leu Gln Ala Arg 165 170 <210> 423 <211> 168 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50164 protein sequence" <400> 423 Met Ser Asn Pro Glu Phe Thr His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Arg Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Thr Leu Val Phe Gly Val Arg Asn Glu Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Met Asn Val Leu Gly Tyr Pro Gly Met Asn His 115 120 125 Gln Val Lys Thr Ile Gly Gly Val Leu Ala Pro Glu Cys Ser Gly Leu 130 135 140 Leu Cys Asp Phe Tyr Arg Met Pro Arg Gln Gln Lys Asn Gln Gln Lys 145 150 155 160 Ala Glu Leu Lys Ser Ser Gly Asp 165 <210> 424 <211> 165 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50165 protein sequence" <400> 424 Met Ser Asp Asn Glu Phe Asn His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asp Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Met Val Leu Gln Asn Tyr Arg Leu Ile Asn Ala Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly His Val Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Val Glu Val Thr Glu Gly Val Leu Arg Glu Gln Cys Ala Gly Met 130 135 140 Leu Cys Asp Phe Tyr Arg Glu Pro Arg Glu Gln Phe Asn Ala Leu Arg 145 150 155 160 Lys Ala Gln Lys Ala 165 <210> 425 <211> 170 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50166 protein sequence" <400> 425 Met Ser Asp Asn Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Met Val Leu Gln Asn Tyr Arg Leu Ile Asp Ala Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Ile Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Gln Val Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Ile Asn Ile Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Val Asp Val Thr Glu Gly Val Leu Ser Glu Arg Cys Ala Asn Met 130 135 140 Leu Cys Asp Phe Tyr Arg Glu Pro Arg Leu Gln Phe Asn Ala Gln Arg 145 150 155 160 Lys Ala Glu Lys Ala Gly Asn Ala Ala Ala 165 170 <210> 426 <211> 169 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50167 protein sequence" <400> 426 Met Ser Asn Pro Glu Leu Thr His Asp His Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Gln Arg Ala Arg Asn Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Gly Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Val Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Gln Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Val Glu Ile Ile Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg His Pro Arg Leu Val Lys Asn Ala Leu Lys 145 150 155 160 Lys Asn Ala Gly Thr Ser Pro Thr Gln 165 <210> 427 <211> 166 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50168 protein sequence" <400> 427 Met Ser Asp Thr Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Met Leu Ala Lys Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Lys Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Asn Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Val Glu Ile Ala Glu Gly Val Leu Ala Asp Glu Cys Ser Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg His Pro Arg Gln Gln Gln Asn Ala Leu Lys 145 150 155 160 Gln Ala Ala Lys His Asp 165 <210> 428 <211> 171 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50169 protein sequence" <400> 428 Met Ser Asp Ile Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Met Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly His Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Ile Glu Phe Thr Glu Gly Val Leu Ala Asp Glu Cys Ser Gly Met 130 135 140 Leu Cys Asp Phe Tyr Arg Tyr Pro Arg Gln Gln Gln Asn Thr Leu Lys 145 150 155 160 Gln Ala Ala Lys Ala Asn Pro Pro Ala Ala Gln 165 170 <210> 429 <211> 165 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50170 protein sequence" <400> 429 Met Ser Asp Asn Glu Leu Asn His Glu Arg Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Tyr Gln Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Gln Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Val Ala Ile Thr Glu Gly Val Leu Ala Glu Ser Cys Ser Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg His Pro Arg Glu Gln Lys Asn Ala Leu Arg 145 150 155 160 Arg Ala Ala Gln Ser 165 <210> 430 <211> 166 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50171 protein sequence" <400> 430 Met Ser Asp Leu Glu Leu Asn Asp Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Ala Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Ala Arg Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Val Glu Ile Ser Glu Gly Val Leu Ala Glu Ser Cys Ser Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg Trp Pro Arg Glu Val Lys Asn Ala Leu Lys 145 150 155 160 Lys Ala Arg Glu Gln Asn 165 <210> 431 <211> 169 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50172 protein sequence" <400> 431 Met Ser Asp Leu Glu Leu Asp His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Leu Leu Ala Lys Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Thr Leu Val Tyr Gly Val Arg Asn Glu Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Met Asn Val Leu Gly Tyr Pro Gly Met Asn His 115 120 125 Gln Val Gln Val Ile Asp Gly Val Leu Ala Pro Glu Cys Ser Gly Leu 130 135 140 Leu Cys Asp Phe Tyr Arg Met Pro Arg Gln Gln Lys Asn Gln Gln Lys 145 150 155 160 Ala Glu Ser Thr Ser Ser Ser Arg Gly Asp 165 <210> 432 <211> 162 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50173 protein sequence" <400> 432 Met Ser Asp Thr Glu Leu Thr His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Met Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Arg Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Gly Arg Ile Gly Thr Leu Val Phe Gly Val Arg Asn Leu Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Val Glu Ile Val Glu Gly Thr Leu Ser Asp Glu Cys Ser Gly Met 130 135 140 Leu Cys Glu Phe Tyr Arg Gln Pro Arg Leu Ala Phe Asn Ala Gln Lys 145 150 155 160 Gln Ala <210> 433 <211> 173 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50174 protein sequence" <400> 433 Met Ser Ile Pro Glu Leu Asn His Asp Val Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Gly Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Gln Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Val Glu Ile Thr Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg Gln Pro Arg Leu Val Lys Asn Ala Leu Lys 145 150 155 160 Lys Pro Ala Gly Asp Pro Ser Ala Leu Gln Asn Asn Arg 165 170 <210> 434 <211> 166 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50175 protein sequence" <400> 434 Met Ser Asp Leu Glu Leu Asn Asp Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Ala Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Ala Arg Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Val Glu Ile Ser Glu Gly Val Leu Ala Gly Ser Cys Ser Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg Trp Pro Arg Glu Val Lys Asn Ala Leu Lys 145 150 155 160 Lys Ala Arg Glu Gln Asn 165 <210> 435 <211> 153 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50176 protein sequence" <400> 435 Met Ser Asp Ile Glu Gln Asn His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Val Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Gly Arg Ile Gly Ser Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Val Glu Met Thr Glu Gly Val Leu Ala Asp Glu Cys Ser Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg His Pro Arg 145 150 <210> 436 <211> 168 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50177 protein sequence" <400> 436 Met Cys Asn Pro Glu Arg Asp His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Thr Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Met Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Thr Leu Val Phe Gly Val Arg Asn Glu Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Leu Asn Val Leu Gly Tyr Pro Gly Met Asn His 115 120 125 Gln Val Lys Thr Ile Gly Gly Val Leu Ala Pro Ala Cys Ser Ala Leu 130 135 140 Leu Cys Asp Phe Tyr Arg Met Pro Arg Gln Gln Lys Asn Gln Gln Lys 145 150 155 160 Ala Glu Leu Lys Leu Ser Asn Asp 165 <210> 437 <211> 162 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50178 protein sequence" <400> 437 Met Ser Ala Ile Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Gly Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Tyr Gln Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Arg Val Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Val Glu Val Thr Glu Gly Val Leu Ala Gly Glu Cys Ser Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg Ala Pro Arg Ala Gln Phe Asn Ala Gln Lys 145 150 155 160 Arg Pro <210> 438 <211> 169 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50179 protein sequence" <400> 438 Met Ser Asn Pro Glu Leu Asn His Glu Tyr Trp Met Arg Tyr Ala Leu 1 5 10 15 Thr Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Glu Arg Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Met Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly His Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Arg Val Ala Ile Thr Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg Gln Pro Arg Gln Val Lys Asn Ala Leu Lys 145 150 155 160 Lys Thr Leu Ser Asp Ser Gln Glu Gln 165 <210> 439 <211> 168 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50180 protein sequence" <400> 439 Met Ser Asn Pro Glu His Asp His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Asn Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Thr Leu Val Tyr Gly Val Arg Asn Glu Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Met Asn Val Leu Gly Tyr Pro Gly Met Asn His 115 120 125 Gln Val Asn Val Ile Gly Gly Val Leu Ala Gln Asp Cys Ser Ala Arg 130 135 140 Leu Cys Asp Phe Tyr Arg Met Pro Arg Gln Gln Lys Asn Gln Gln Arg 145 150 155 160 Ala Glu Leu Lys Ala Gln Gly Asp 165 <210> 440 <211> 168 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50181 protein sequence" <400> 440 Met Ser Asp Pro Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu 1 5 10 15 Gln Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Ile His 85 90 95 Ser Arg Ile Gly Thr Val Val Tyr Gly Val Arg Asn Glu Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Leu Asn Val Leu Ser Tyr Pro Gly Met Asn His 115 120 125 Gln Val Lys Val Ile Gly Glu Val Leu Ala Pro Ala Cys Ser Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg Met Pro Arg Gln Gln Lys Asn Gln Gln Lys 145 150 155 160 Ala Glu Trp Lys Leu Ser Gly Glu 165 <210> 441 <211> 171 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50182 protein sequence" <400> 441 Met Ser Asn Pro Glu Leu Asn His Glu Tyr Trp Met Arg Tyr Ala Leu 1 5 10 15 Thr Leu Ala Lys Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala 20 25 30 Val Leu Val Tyr His Asp Gln Val Ile Gly Glu Gly Trp Asn Arg Ala 35 40 45 Ile Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg 50 55 60 Gln Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu 65 70 75 80 Tyr Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His 85 90 95 Ser Arg Ile Gly Arg Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly 100 105 110 Ala Ala Gly Ser Leu Leu Asn Val Leu Asn Tyr Pro Gly Met Asn His 115 120 125 Gln Ile Asp Met Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met 130 135 140 Leu Cys Asp Phe Tyr Arg Leu Pro Arg Ile Val Lys Asn Ala Leu Lys 145 150 155 160 Gln Ser Pro Pro Asp Ser Thr Asn Leu His Ala 165 170 <210> 442 <211> 32 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="L32 Linker sequence" <400> 442 Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Ser Glu Thr Pro Gly Thr 1 5 10 15 Ser Glu Ser Ala Thr Pro Glu Ser Ser Gly Gly Ser Ser Gly Gly Ser 20 25 30 <210> 443 <211> 507 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50140" <400> 443 atgtctgatc tggaactgaa tcacgagtac tggatgcggc acgccctgca actggccaag 60 cgggccagag atgagggcga ggtgccagtg ggcgccgtgc tggtgctgaa caaccaggtc 120 atcggagaag gctggaacag agccatcggc ctgcatgacc ccacagccca tgccgaaatc 180 atggccctga gacagggcgg actggtgctg cagaactata ggctgattga caccaccctg 240 tacgtgacct tcgagccttg tgtgatgtgc tccggcgcta tggtgcacag cagaatcggc 300 acactggtct ttggcgttag aaacagcaag cgcggagctg ctggcagcct gatgaatgtg 360 ctgaactacc ccggcatgaa ccaccaggtg caaatcatcg acggcgtgct cgcccctgaa 420 tgcagcggac tgctgtgcga cttctaccgg atgcctagac aggtgttcaa ccagcagaaa 480 gccgagagca cctctatcaa cggcgac 507 <210> 444 <211> 492 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50141" <400> 444 atgtccaacc ccgagctgac ccacgagcac tggatgagat acgccctgac actggccaag 60 cgggccagag aggaaggcga agtgccagtg ggcgccgtgc tggtgctgaa caaccaggtg 120 atcggagaag gctggaatag agccattgga ctgcatgatc ctacagccca cgccgaaatc 180 atggccctga gacagggcgg cctggtgctg cagaactata gactgatcga caccaccctg 240 tacgtgacat tcgagccttg tgtgatgtgc gccggcgcca tggtgcacag cagaatcggc 300 cagctggtct ttggcgtgcg gaacagcaaa cggggcgctg caggctctct gatgaatgtg 360 ctcaactacc ccggcatgaa ccacagaatc gagttcaccg agggagttct gcgggacgag 420 tgcgctgcta tgctgtgcga cttctaccgc cagcctagac aagtgttcaa cgccctgaag 480 accggcaacg cc 492 <210> 445 <211> 507 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50142" <400> 445 atgagcatcc ccgagctgaa ccacgacgtg tggatgcggc acgctcttac actggccaag 60 cgggccagag aagaaggcga agtgccagtg ggcgccgtgc tggttctgaa cggccaggtg 120 atcggcgagg gctggaacag agccattgga ctgcatgacc ctaccgccca cgccgagatc 180 atggccctga gacagggcgg actggtgctg cagaactatc ggctgatcga caccaccctg 240 tacgtgacct tcgagccttg cgtgatgtgc gccggcgcta tggtgcacag cagaatcggc 300 cagctggtgt tcggcgtgcg gaactccaag aggggcgccg ctggatctct gatcaacgtg 360 ctgaattacc ccggcatgaa ccatagagtc gccatcacag agggagtgct cagagaggaa 420 tgtgccgcca tgctgtgcga cttctacaga caacctagac aggtctttaa cgccctgaag 480 aaacctgctg gcgatatcaa tgccttc 507 <210> 446 <211> 516 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50143" <400> 446 atgagcaacc ccgagctgaa tcacgagtac tggatgcggt acgccctgac actggccaag 60 cgggccagag atgaaggcga agtgcctgtg ggcgccgtgc tggtgctgaa cgaccaggtg 120 atcggagaag gctggaatag agccattggc ctgcatgacc ccaccgccca cgccgagatc 180 atggccctga gacagggcgg actggttctg cagaactacc gcctgatcga caccaccctg 240 tacgtgacat tcgagccttg tgtgatgtgc gccggcgcca tggtgcattc tagaatcggc 300 agactggtgt tcggcgtgcg gaacagcaag aggggcgctg ctggcagcct gctgaacgtg 360 ctcaattatc ctggaatgaa ccaccacatc gagatggaag agggcgtgct gcgggacgag 420 tgcgccgcta tgctgtgcga cttctacaga cagcctagac aggtctttaa cgccctgaag 480 aaatccccac ctgatatcaa caacctgcaa gctaga 516 <210> 447 <211> 507 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50144" <400> 447 atgagcaacc ctgagctgac acacgaccac tggatgagac acgccctgac cctggcccag 60 cgggccagaa acgagggcga agtgcccgtg ggcgctgtgc tggtgctgaa tggccaagtg 120 atcggagaag gctggaacag agccatcggc ctgcatgacc caacagccca cgccgagatc 180 atggccctgc ggcagggcgg actggtcctc cagaactatc ggctgatcga caccgtgctg 240 tacgtgacct tcgagccttg tgtgatgtgc gccggcgcca tggtgcactc tagaatcgga 300 cagctggtct ttggcgtgcg gaatagcaag cgcggcgccg ctggctccct gatcaacgtg 360 cttaattacc ccggcatgaa ccacagagtg gaaattatcg agggcgttct gagagatgag 420 tgcgcagcta tgctgtgcga cttctacaga catcctagac aggtgttcaa cgccctgaaa 480 aagaacgccg gaaccatcaa cacccag 507 <210> 448 <211> 498 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50145" <400> 448 atgagcgaca ccgagctgaa ccacgagtac tggatgcggc acgccctgat gctggctaag 60 cgggccagag atgagggcga agtgcctgtg ggcgccgtgc tggtcctgaa aaaccaggtg 120 atcggagaag gctggaatag agccatcggc ctgcatgacc ccaccgccca cgctgaaatc 180 atggccctga gacagggagg cctggtgctc cagaactata gactgattga taccacactg 240 tacgtgacat tcgagccttg tgtgatgtgc gccggcgcca tggtgcactc tagaatcggc 300 aacctggtct ttggcgtgcg gaacagcaag aggggcgctg ctggcagcct gatcaacgtg 360 ctgaattacc ccggcatgaa ccacagagtg gaaatcgccg agggagttct ggccgacgag 420 tgctccgcca tgctgtgcga cttctaccgg catcctagac aagtgttcaa cgccctgaag 480 caggccgcca agcacatc 498 <210> 449 <211> 513 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50146" <400> 449 atgagcgaca tcgagctgaa tcacgagtac tggatgcggc acgccctgat gctggccaaa 60 agagccagag aggaaggaga agtgccagtg ggcgccgtgc tggtgctgaa caaccaggtg 120 atcggcgaag gctggaaccg ggccattggc ctgcatgatc ctaccgccca cgccgagatc 180 atggccctga gacagggcgg actggtgctc cagaactata gactgatcga cacaacactg 240 tacgtgacct tcgagccttg tgtgatgtgc gccggcgcca tggtgcacag cagaatcggc 300 cacctggtct ttggcgttag aaactctaag cgcggagctg ctggctccct gatcaatgtg 360 ctgaactacc ccggcatgaa ccaccggatc gaattcaccg agggcgtgct ggctgatgaa 420 tgcagcggca tgctgtgcga cttctacaga taccctagac aagtgttcaa caccctgaag 480 caggccgcta aggccatcaa ccccgccgcc cag 513 <210> 450 <211> 519 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50147" <400> 450 atgagcatcc ctgagctgaa tcacgatgtg tggatgcggc acgccctgac actggctaag 60 agagccaggg aagagggcga agtgccagtg ggagccgtgc tggtgctgaa cggccaggtg 120 atcggagaag gctggaaccg ggccatcggc ctgcatgacc ccaccgccca cgccgagatt 180 atggccctga gacagggcgg actggtcctt caaaattata gactgatcga caccaccctg 240 tacgtgacat tcgagccttg tgtgatgtgc gccggagcca tggtgcactc tagaatcggc 300 cagctggtgt tcggcgtgcg caacagcaag cggggcgctg ctggctccct gatgaacgtg 360 ctgaactacc ccggcatgaa tcatagagtg gaaatcaccg agggcgttct cagagatgag 420 tgcgccgcta tgctgtgcga cttctaccgg cagcctagac aggtctttaa cgccctgaag 480 aaacctgccg gcgacatcaa cgccctgcag aacaacaga 519 <210> 451 <211> 504 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50148" <400> 451 atgagcaacc ccgagttcac acacgagtac tggatgcggc acgccctgac actggcccgc 60 agagccagag atgagggcga agtgcctgtg ggcgccgtgc tggtcctgaa caaccaggtg 120 atcggcgaag gctggaaccg ggccattgga ctgcatgacc ccaccgccca cgccgaaatc 180 atggccctga gacagggcgg actggtgctg cagaactacc ggctgatcga caccaccctg 240 tacgtgacat tcgagccatg tgtgatgtgt agcggcgcta tggtccattc tagaatcggc 300 accctggttt tcggcgtgcg gaacagcaag agaggagctg ctggcagcct gatgaacgtg 360 ctgaattatc ctggaatgaa tcaccaggtg aagaccatcg gcggcgtgct cgcccctgaa 420 tgcagcggcc tgctgtgcga cttctacaga atgcctagac aagtgtttaa ccagcagaaa 480 gccgagctga agtccatcaa cgac 504 <210> 452 <211> 501 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50149" <400> 452 atgagcgacg ccgagctgac ccacgagtac tggatgagac acgccctgac actggcccag 60 cgcgccagag atgagggaga agtgccagtg ggcgccgtgc tggttctgaa caaccaggtg 120 atcggcgagg gctggaatag agccatcggc ctgcatgacc ccaccgccca tgctgaaatc 180 atggccctgc ggcagggcgg cctggtgcaa cagaactaca gactgatcga caccaccctg 240 tacgtgacat tcgagccttg tgtgatgtgc gccggagcta tggtgcactc caggatcgga 300 agactgatct tcggcgtgcg gaacagcaag cggggcgcag ctggatctct gattaacgtg 360 ctgaattatc ctggcatgaa ccacagagtg gaagtggtgg aaggcatcct gagagatgag 420 tgcgccggca tgctgtgcga cttctaccgg caacctagac aggtctttaa cgccctcaag 480 aaaggcgcca ccgacatcaa c 501 <210> 453 <211> 501 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50150" <400> 453 atgagcgacg ccgagctgac ccacgagtac tggatgagac acgccctgac actggcccag 60 agagctaggg atgagggaga agtccccgtg ggtgctgttc tggtgctcaa caaccaggtg 120 atcggagagg gctggaatag agccatcggc ctgcatgatc ctacagccca cgccgaaatc 180 atggccctga gacagggcgg actggtccag cagaactatc ggctgctgga caccaccctg 240 tacgtgacct tcgagccatg tgtgatgtgc gccggcgcca tggtgcactc tagaatcggc 300 agactgatct tcggcgtgcg gaacagcaag cggggcgccg ctggctccct gattaacgtg 360 ctgaattacc ctggcatgaa ccacagagtg gaagtggtgg aaggcatcct gcgggacgag 420 tgcgccggca tgctgtgcgc tttttaccgc caacctagag ccgtgaagaa cgccctgaaa 480 aagggcgcca ccgacgtgct g 501 <210> 454 <211> 507 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50151" <400> 454 atgagcgacc tggaactgaa ccacgagtac tggatgagac acgccctgca actggcccag 60 agggccagag atgagggaga agtgccagtg ggcgccgtgc tggtctacaa caaccaggtt 120 atcggcgaag gctggaatag agccattggc ctgcatgacc ccaccgccca tgctgaaatc 180 atggccctgc ggcagggcgg actggtgctc cagaactacc ggctgctgga caccaccctg 240 tatgtgacct ttgagccttg tgtgatgtgc tccggcgcca tggtgcacag cagaatcgga 300 acactggtgt tcggcgtgcg gaacgagaag cggggcgctg ctggcagcct gatgaacgtg 360 ctgagatacc ccggcatgaa tcaccaggtg caaatcatcg acggcgtgct ggcccctgaa 420 tgcagcggcc tgctgtgcga cttctacaga atgcctagac agcagaaaaa ccagcaaaag 480 gccgagtcta catctagccc tggagat 507 <210> 455 <211> 501 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50152" <400> 455 atgagcgaca acgagctgaa ccacgagtac tggatgcggc acgccctggg cctcgccaaa 60 agagccagag aggaaggcga ggtgcccgtg ggcgctgttc tggtcctgaa caaccaggtg 120 atcggagaag gctggaacag ggccatcggc ctgcatgacc caacagccca cgccgagatc 180 atggctctga gacagggcgg cctggtgctg cagaactata gactgacaga taccaccctg 240 tacgtgacct ttgagccttg tgtgatgtgc gccggagcaa tggtccacag cagaatcggc 300 accctggtgt tcggcgtgcg gaacagcaag cggggcgccg ccggctctct gatgaacgtg 360 ctgaattacc ccggcatgaa tcatagagtg gaaattgtgg aaggaatcct gagcgagtcc 420 tgcgccgcca tgctgtgcga cttctaccgg caacctagag ccgtgaagaa cgccctgaag 480 aaggccgctg atcctgccgc t 501 <210> 456 <211> 492 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50153" <400> 456 atgagcgata cagaattcac ccacgagcac tggatgagac acgccctgac actggctcaa 60 agagcccggg acgagggcga agtgccagtg ggagccgtgc tcgtgctgaa caaccaggtt 120 atcggcgaag gctggaatag agccatcggc ctgcatgacc ctaccgccca cgccgagatc 180 atggccctga gacagggcgg cctggtcctg cagaactata ggctgctgga caccaccctg 240 tacgtgacat ttgagccttg tgtgatgtgc gccggcgcaa tggtgcacag cagaatcgga 300 catctggtgt tcggcgtgcg gaacagcaag cggggcgcca tcggatctct gatgaacgtg 360 ctgggctacc ccggcatgaa tcaccaggtc caggtgtccg agggcgtgct ggccaccgaa 420 tgcagcgcta tgctgtgcga cttctaccgg gctcctagac tggtgaaaaa cgccctgaag 480 gaaaaggcca ga 492 <210> 457 <211> 513 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50154" <400> 457 atgagcgagt ccgagttcac ccacgagcac tggatgcggc acgccctgac actggccaga 60 agagccagag aggaaggcga ggtgccagtg ggagctgtgc tggtgctgaa caaccaggtg 120 atcggagaag gctggaacag agccatcggc ctgcatgatc ctaccgccca cgccgagatc 180 atggccctga gacagggcgg cctcgtcctg cagaactacc ggctgctgga cagcaccctg 240 tatgtgacat tcgagccctg tgtgatgtgc gccggcgcta tggtgcacgg cagaatcgga 300 aatctggtct ttggcgtgcg gaacagcaag cggggcgcca ttggatctct gatgaatgtg 360 gtgggctacc ccggcatgaa ccaccaaatc aacgtgatcg agggcgttct tgcagaagaa 420 tgcagcgcca tgctgtgcga cttctacaga gcccctagac tggtgaaaaa cgccctgaag 480 gaaaaggcca gaaacggcaa caatcctaac aag 513 <210> 458 <211> 492 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50155" <400> 458 atgagcaacc ccgagctgac acacgagcac tggatgagat acgccctgac actggccaag 60 cgggccagag aggaaggcga agtgccagtg ggcgccgtgc tggttctgaa caaccaggtg 120 atcggcgaag gctggaacag agccatcggc ctgcatgatc ctaccgccca cgccgaaatc 180 atggccctga gacagggcgg actggtgctc cagaactata gactgatcga caccaccctg 240 tacgtgacct tcgagccttg tgtgatgtgc gccggagcta tggtgcactc cagaattggc 300 cagctggtgt tcggcgtgcg gaacagcaag aggggcgctg ctggctctct gatgaatggtg 360 ctgaattacc ccggcatgaa ccacagaatc gagtttacag agggagtgct gcgggacgag 420 tgcgccgcta tgctgtgcga cttctaccgg caacctagac tggtcaagaa cgccctgaaa 480 accggcaacg cc 492 <210> 459 <211> 498 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50156" <400> 459 atgagcgatc ctgagctgaa tcatgaatat tggatgagac acgccctgca gctggctaaa 60 agagccagag aggaaggcga agtgcccgtg ggagccgtgc tcgtgctgaa caaccaggtt 120 atcggcgagg gctggaacag agccatcggc ctgcatgacc ccaccgccca cgccgaaatc 180 atggccctgc ggcagggagg cctggtgctg cagaactacc ggctgctgga caccacactg 240 tacgtgacct tcgagccttg cgtgatgtgt agcggagcta tgatccactc tagaatcggc 300 acagtggtct ttggcgtgcg gaacgagaag cgcggcgccg ccggcagcct gctgaatgtg 360 ctgagatacc caggcatgaa ccaccaggtg aacgtgctgg gcggcgtcct ggcccctgct 420 tgttccgaga tgctgtgcga attctacaga atgcctagac agcagaagaa ccggcaaaag 480 gccgagagca agctgagc 498 <210> 460 <211> 498 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50157" <400> 460 atgagcgaca acgagctgaa tcacgagcac tggatgcggc acgccctgac actggcccag 60 cgcgccagag aggaaggcga ggtgcctgtg ggcgccgtgc tggtgctgca aaaccaggtg 120 atcggagaag gctggaatag agccatcggc ctgcatgacc ccaccgccca tgccgagatc 180 atggccctga gacagggcgg catggtgctg cagaactacc ggctgatcga caccaccctg 240 tacgtgacct tcgagccatg tgtgatgtgc gccggcgcca tggtccactc tagaatcggc 300 cagctggtct ttggcgtgcg gaacagcaag cggggcgctg ctggcagcct gattaacgtg 360 ctgaactatc ctggaatgaa ccacagagtg gaaatcacag agggagtgct ggctgatgat 420 tgcagcagca tgctgtgcga cttctacaga caccctagag aacagaagaa cgccctcaaa 480 agagccgctc actccaac 498 <210> 461 <211> 504 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50158" <400> 461 atgagcaacc ccgagcacaa ccacgagtac tggatgcggc acgccctgac cctggcccag 60 agggccagag atgagggaga agtgccagtg ggcgccgtgc tggtctacaa caaccaggtt 120 atcggcgaag gctggaacag agccatcgga cttcatgatc ctaccgccca cgctgaaatc 180 atggccctga gacagggcgg cctggtgctg cagaactacc ggctgctgga cacaaccctg 240 tatgtgacct ttgagccttg tgtgatgtgt agcggcgcta tggtgcactc tagaatcgga 300 acactggtgt tcggcgtgcg caacgagaag cggggcgccg ctggcagcct gatgaacgtg 360 ctgggctacc ccggcatgaa tcaccaggtg caaaccatcg gcggagtgct cgcccctgag 420 tgctccggcc tgctgtgcga cttctacaga atgcctagac aacagaaaaa ccagcagaag 480 gccgaactga atcaacctgg cgac 504 <210> 462 <211> 504 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50159" <400> 462 atgagcgacc tggaactgaa tcacgagtac tggatgagac acgccctgag cctggctaag 60 agagccagag atgagggcga agtgcccgtg ggcgccgtgc tggtgctgaa caaccaggtt 120 atcggcgagg gatggaaccg ggccattggc ctgcatgacc ccaccgccca cgctgaaatc 180 atggccctga ggcagggcgg actggtgctc cagaactaca gactgctgga caccaccctg 240 tacgtgacat tcgagccatg tgtgatgtgc tctggcgcta tggtgcattc tagaatcgga 300 acactggtct acggcgtgcg gaacgagaag cggggcgccg ccggcagcct gatgaatgtg 360 ctgggctatc ctggcatgaa ccaccaggtg caaatcatcg gcggcgtgct ggcccctgac 420 tgcagcggcc tgctgtgcga cttctaccgc atgcctagac aacagaaaaa ccagcagaag 480 gccgagctga agtccagcgg agat 504 <210> 463 <211> 498 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50160" <400> 463 atgtctgatc acgagttcaa cgatgagtac tggatgcggc acgccctgac cctggctaaa 60 agagccaggg aagagggcga ggtgcctgtg ggcgccgtgc tggtgctgaa caaccaggtg 120 atcggagaag gatggaatag agccatcggc ctgcatgacc ccaccgccca tgctgaaatc 180 atggccctga gacaaggagg cctggtcctc cagaactatc gcctgatcga cgccacactg 240 tacgtgacct ttgagccttg tgtgatgtgc gccggcgcca tggtgcacag cagaatcagc 300 cggctggttt tcggcgtgcg gaacagcaag cggggcgctg ctggcagcct gattaacgtg 360 ctgaattacc ccggcatgaa ccacagagtg gaaatcacag agggcatcct ggccgagtcc 420 tgcagcgcca tgctgtgcga cttctacaga tggcctagag aggtgaagaa cgccctgaag 480 aaggccagac aggaggaa 498 <210> 464 <211> 498 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50161" <400> 464 atgagccaga ccgaactgac ccacgagtat tggatgcggc acgccctgac actggcccaa 60 agagccagag acgagggcga agtgccagtg ggcgccgtgc tggtgctgaa caaccaggtc 120 atcggcgaag gctggaatag ggccattgga ctgcatgatc ctaccgccca cgccgagatc 180 atggccctga gacagggcgg cctggtcctc cagaactacc ggctgctgga caccaccctg 240 tacgtgacct tcgagccttg tgtgatgtgc gccggagcta tggtgcacgg cagaatcgga 300 acactggtgt tcggcgtgcg gaacagcaaa agaggcgctg ttggatctct gatgaatatc 360 acaggctacc ccggcatgaa ccaccaggtg caagtgatcg agggcatcct ggctacagag 420 tgctccgcca tgctgtgcgc tttttaccgc cagcctagac tggtgaagaa cgccctgaag 480 gaagccgcca agaccgcc 498 <210> 465 <211> 501 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50162" <400> 465 atgagcaacc ccgagctgaa ccatgattac tggatgcggc acgccctgag cctggccaag 60 cgggccagag aggaaggcga agtgccagtg ggcgccgtgc tggtgcggaa caacgaggtg 120 atcggcgagg gatggaacag agccatcggc ctgcatgacc ctacagccca cgccgagatc 180 atggccctga gacagggcgg catggtcctc cagaactata gactgatcga caccaccctg 240 tacgtgacct tcgagccttg tgtgatgtgc gccggcgcca tggtgcacag cagaatcggc 300 cagctggtct ttggcgttag aaattctaag cgcggagctg ctggttccct gatgaacgtg 360 ctgaattacc ccggcatgaa ccacagagtg gaaatcgtgg aaggcgtgct gcgggacgag 420 tgcgccggaa tgctgtgcga cttctacagg caacctagac tggtgaagaa cgcccagaaa 480 aagggcgctg aacctctgat t 501 <210> 466 <211> 516 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50163" <400> 466 atgagcaacc ccgagctgaa tcacgagtac tggatgagat acgccctgac cctggccaag 60 agagccagag acgaaggaga ggtgcctgtg ggcgctgttc tggtgtacaa cgaccaggtg 120 atcggcgaag gctggaaccg ggccatcggc ctgcatgacc ccaccgccca cgccgagatt 180 atggccctgc gccagggcgg cctggtgctg cagaactacc ggctgatcga cacaaccctg 240 tacgtgacat ttgagccctg cgtgatgtgc gccggagcaa tggtgcacag cagaatcggc 300 agactggtgt tcggcgtgcg gaacagcaag cggggcgctg ctggctctct gctgaacgtg 360 ctcaattatc ctggaatgaa ccatcacatc gagatggaag aaggcgtgct gagagatgag 420 tgcgccgcca tgctgtgtga tttctacaga caacctagaa tggtcaagaa cgcccttaaa 480 aagtccccac ctgacagccc taatctgcag gccaga 516 <210> 467 <211> 504 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50164" <400> 467 atgagcaacc ccgaattcac ccacgagtac tggatgagac acgccctgac cctggctaga 60 cgcgcccggg acgagggcga ggtgccagtg ggcgctgtgc tggtcctcaa caaccaggtg 120 atcggcgaag gctggaatag agccatcggc ctgcatgatc ctacagccca cgctgaaatc 180 atggccctga gacagggcgg cctggtgctg cagaactacc ggctgctgga caccaccctg 240 tacgtgacat ttgagccttg tgtgatgtgt agcggcgcca tggtgcactc tagaatcgga 300 acactggtgt tcggcgtgcg gaacgagaag cggggcgccg ccggcagcct gatgaatgtg 360 ctgggatatc ccggcatgaa ccaccaggtt aagaccatcg gaggcgtgct ggcccctgaa 420 tgcagcggac tgctgtgcga cttctacaga atgcctagac agcaaaagaa ccagcagaaa 480 gccgagctga agtccagcgg cgat 504 <210> 468 <211> 495 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50165" <400> 468 atgagcgaca acgagttcaa ccacgagtac tggatgagac acgccctgac cctggcccag 60 cgcgccagag atgagggcga ggtgcctgtg ggcgccgtgc tggtcctcga taaccaggtg 120 atcggagaag gctggaatag agccatcggc ctgcatgacc ctaccgccca cgccgagatc 180 atggccctga ggcagggcgg catggtcctg cagaactata gactgatcaa cgctacactg 240 tacgtgacct tcgagccttg cgtgatgtgc gccggcgcta tggttcattc tagaatcggc 300 cacgtggtgt tcggcgtgcg gaacagcaag cggggcgccg ctggcagcct gatgaacgtg 360 ctgaactacc ccggcatgaa tcacagagtg gaagtgacag agggagtgct gcgggaacag 420 tgtgccggca tgctgtgcga cttctaccgg gaaccaagag aacaatttaa cgccctgaga 480 aaggctcaga aagcc 495 <210> 469 <211> 510 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50166" <400> 469 atgagcgaca acgagctgaa tcacgagtac tggatgagac acgccctgac cctggcccag 60 cgggccagag atgagggaga agtgcccgtg ggcgccgtgc tcgtgctgaa caaccaggtt 120 atcggcgaag gctggaatag agccatcggc ctgcatgatc ctaccgccca cgctgaaatc 180 atggccctga gacagggcgg aatggtcctg cagaactata gactgatcga cgccacactg 240 tacgtgacat tcgagccatg tatcatgtgc gccggcgcca tggtgcactc tagaatcggc 300 caggtggtgt tcggcgtgcg caacagcaag cggggcgctg ccggctccct gattaacatc 360 ctgaactacc ctggcatgaa ccacagagtg gacgtgaccg agggcgtgct gagcgagcgg 420 tgcgccaaca tgctgtgcga cttctaccgg gaacctagac tgcaatttaa cgcccagaga 480 aaggccgaga aagccggaaa tgccgctgct 510 <210> 470 <211> 507 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50167" <400> 470 atgagcaacc ccgagctgac ccacgaccac tggatgcggc acgccctgac cctggcccag 60 agagccagaa acgagggaga agtgcctgtg ggcgctgttc tggtgctgaa cggccaagtg 120 atcggcgaag gctggaacag agccatcggc ctgcatgacc ctaccgccca cgccgagatc 180 atggccctgc ggcagggcgg actggtcctc cagaactacc ggctgatcga caccgtgctg 240 tacgtgacct ttgagccttg tgtgatgtgc gctggcgcca tggtccattc tagaatcggc 300 cagctggtgt tcggcgtgcg caatagcaag cggggtgccg ccggcagcct gattaacgtg 360 ctgaactatc ctggcatgaa ccacagagtg gaaatcatcg agggcgtgct gagagatgag 420 tgcgcagcta tgctgtgcga cttctacaga caccccagac tggtgaagaa cgccctgaaa 480 aagaatgccg gaacatcccc aacacag 507 <210> 471 <211> 498 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50168" <400> 471 atgagcgaca cagagctgaa ccacgagtac tggatgcggc acgccctgat gctggctaaa 60 cgcgccagag atgagggaga agtgccagtg ggcgccgtgc tggtgctgaa gaaccaggtg 120 atcggcgaag gctggaacag agccatcgga ctgcatgacc ctacagccca cgctgaaatc 180 atggccctga gacagggcgg cctggtcctc cagaactata gactgatcga caccaccctg 240 tacgtgacct ttgagccttg tgtgatgtgc gccggcgcta tggtgcactc tagaatcgga 300 aatctggttt tcggcgtgcg gaacagcaag cggggcgccg ctggctccct gattaacgtg 360 ctgaattacc ccggcatgaa ccacagagtg gaaatcgccg agggcgtgct ggccgacgaa 420 tgcagcgcca tgctgtgcga cttctaccgg catcctagac agcagcaaaa cgccctgaag 480 caggccgcca agcacgat 498 <210> 472 <211> 513 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50169" <400> 472 atgagcgaca tcgagctgaa tcacgagtac tggatgagac acgccctgat gctggccaag 60 agagccagag aggaaggcga agtgcctgtg ggcgccgtgc tggtgctgaa caaccaggtg 120 atcggagaag gatggaaccg ggccatcggc ctgcatgatc ctacagccca cgccgagatc 180 atggccctga ggcagggcgg actggtcctc cagaactaca gactgatcga caccaccctg 240 tacgtgacct ttgagccatg tgtgatgtgc gccggcgcca tggtgcacag cagaatcggc 300 cacctggttt tcggcgtgcg gaacagcaag cggggcgctg ctggctccct gattaacgtg 360 ctgaactatc ctggcatgaa ccacagaatc gaattcaccg agggcgtgct ggctgatgag 420 tgctctggca tgctgtgcga cttctacaga taccctagac agcagcaaaa tacactgaag 480 caggccgcta aagccaaccc ccccgccgcc cag 513 <210> 473 <211> 495 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50170" <400> 473 atgagcgaca acgagctgaa ccacgagaga tggatgcggc atgccctgac cctggctcaa 60 agagccagag atgagggcga ggtgccagtg ggcgctgtgc tggtctacca gaaccaggtg 120 atcggcgaag gctggaacag agccattggc ctgcatgacc ctaccgccca cgccgagatc 180 atggccctga gacagggcgg actggttctg cagaattacc ggctgatcga cacaaccctg 240 tacgtgacct ttgagccttg tgtgatgtgc gccggcgcca tggtgcactc tagaatcgga 300 cagctggtgt tcggcgtgcg gaacagcaag cggggcgccg ccggcagcct gatcaacgtg 360 ctcaattatc ctggcatgaa ccacagagtg gccatcacag aaggagtgct ggccgaatcc 420 tgcagcgcca tgctgtgcga cttctacaga caccccagag aacagaagaa cgccctgagg 480 cgggctgctc agagc 495 <210> 474 <211> 498 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50171" <400> 474 atgagcgatc tggaactgaa cgacgagtac tggatgcggc acgctctgac cctggccaag 60 cgggccagag aagagggaga agtccccgtg ggcgccgtgc tcgttctgaa caaccaggtg 120 atcggcgagg gctggaacag agccattgga ctgcatgatc ctaccgccca cgccgagatc 180 atggccctga gacagggcgg cctggtcctg caaaattata gactgatcga cgccaccctg 240 tacgtgacat ttgagccttg tgtgatgtgc gccggcgcta tggtgcacag cagaatcgcc 300 aggctggtgt tcggcgtgcg gaacagcaag cgcggcgccg ctggatctct gatgaacgtg 360 ctgaattacc caggcatgaa ccacagagtg gaaatcagcg agggcgtgct ggctgagtcc 420 tgcagcgcca tgctgtgcga cttctacaga tggcctagag aggtgaagaa cgccctgaaa 480 aaggcccggg aacagaac 498 <210> 475 <211> 507 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50172" <400> 475 atgagcgacc tggaactgga tcacgagtac tggatgcggc acgccctgct gctggctaaa 60 agagccagag atgagggcga agtgcccgtg ggcgccgtgc tggtgctcaa caaccaggtc 120 atcggagaag gctggaatag agccatcggc ctgcatgacc caacagccca tgccgaaatc 180 atggccctga ggcagggcgg cctggtgctg cagaactaca gactgctgga caccacactg 240 tatgtgacct tcgagccttg tgtgatgtgc tctggcgcta tggtgcactc tagaatcgga 300 accctggtct acggcgtgcg gaacgagaag cggggcgccg ctggctccct gatgaacgtg 360 ctgggctacc ccggtatgaa tcaccaggtg caagtgatcg acggcgtgct ggcccctgaa 420 tgcagcggac tgctgtgcga cttctaccgg atgcctagac agcaaaagaa ccagcagaag 480 gccgagagca ccagcagcag aggcgac 507 <210> 476 <211> 486 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50173" <400> 476 atgagcgaca ccgagctgac ccacgagtac tggatgcggc acgccctgat gctggctcaa 60 agagccagag atgaaggcga agtgccagtg ggagccgtgc tggtcctgaa caaccgggtg 120 atcggcgagg gctggaacag agctatcgga ctgcatgatc ctacagccca cgccgagatc 180 atggccctga gacagggcgg cctggtgctg cagaactacc gcctgctgga caccaccctg 240 tacgttacat ttgagccttg tgtgatgtgc gccggcgcta tggtgcacgg cagaatcggc 300 acactggtgt tcggcgtgcg gaacctgaag cggggcgccg ccggatctct gatgaatggg 360 ctgaattatc ctggcatgaa ccacagagtg gaaatcgtgg aaggaaccct ctccgacgaa 420 tgcagcggca tgctgtgcga gttctacaga cagcccagac tggccttcaa cgcccagaag 480 caggcc 486 <210> 477 <211> 519 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50174" <400> 477 atgtctatcc ccgagctgaa tcacgatgtg tggatgagac acgctctgac actggccaag 60 agggctagag aggaaggcga agtgccagtg ggcgccgtgc tggttctgaa cggccaagtg 120 atcggagaag gatggaacag agccatcggc ctgcatgacc ccaccgccca cgccgagatt 180 atggccctgc gccagggcgg cctggtgctc cagaactaca gactgatcga cacaaccctg 240 tacgtgacct tcgagccttg tgtgatgtgc gccggcgcta tggtgcacag cagaatcggc 300 cagctggtct ttggcgtgcg gaacagcaag cggggcgccg ctggttccct gatgaacgtg 360 cttaattatc ctggcatgaa ccatagagtg gaaatcaccg agggagtgct gagagatgag 420 tgcgccgcca tgctgtgcga cttctaccgg cagcctagac tggtcaagaa cgccctgaag 480 aaacctgccg gcgaccctag cgccctgcag aacaaccgg 519 <210> 478 <211> 498 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50175" <400> 478 atgagcgatc tggaactgaa tgatgagtac tggatgcggc acgccctgac actggccaag 60 agagccagag aagagggcga agtgcctgtc ggcgccgtgc tggtgctgaa caaccaggtg 120 atcggcgagg gctggaaccg ggccatcgga ctgcatgacc ccaccgccca tgccgagatt 180 atggccctga gacagggcgg cctggttctg caaaattatc gcctgatcga cgccaccctg 240 tacgtgacct tcgagccttg tgtgatgtgc gccggagcta tggtgcacag cagaatcgcc 300 aggctggtct ttggcgtgcg gaacagcaag cggggcgctg ctggctccct gatgaacgtg 360 ctgaactacc caggcatgaa ccacagagtg gaaatcagcg agggagtgct cgctggctct 420 tgcagcgcca tgctgtgcga cttctacaga tggcctagag aagtgaagaa cgccctgaag 480 aaagccagag agcagaac 498 <210> 479 <211> 459 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50176" <400> 479 atgagcgaca tcgagcagaa ccacgagtac tggatgcggc acgccctggt tctggccaag 60 cgggccagag aggaaggcga agtgccagtg ggcgccgtgc tggtgctgaa caaccaggtg 120 atcggcgagg gctggaacag ggccatcggc ctccatgatc ctaccgccca cgccgaaatc 180 atggccctga gacagggcgg actggtcctg caaaattacc ggctgatcga cacaaccctg 240 tacgtgacat tcgagccttg tgtgatgtgc gccggcgcta tggtgcacgg cagaatcggc 300 agcctggtct ttggcgtgcg gaacagcaag agaggcgccg ctggctctct gattaacgtg 360 ctgaattatc ctggaatgaa ccacagagtg gaaatgaccg agggcgtgct ggctgatgaa 420 tgcagcgcca tgctgtgcga cttctacaga caccccaga 459 <210> 480 <211> 504 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50177" <400> 480 atgtgcaacc ctgagagaga tcacgagtac tggatgcggc acgccctgac actggcccag 60 cgggccagag atgagggcga agtgcctgtg ggcgccgtgc tggtgctgaa caaccaggtt 120 atcggcgaag gatggaatag agccatcggc ctgcatgacc ccaccgccca tgccgaaatc 180 atggccctga gacagggcgg catggtgctg cagaactaca gactgctgga caccaccctg 240 tacgtgacct ttgagccctg cgtgatgtgt tccggcgcca tggtccactc tagaatcggt 300 acactggtgt tcggcgtgcg gaacgagaag cggggcgctg ctggcagcct gctgaatgtg 360 ctgggatatc ctggcatgaa ccaccaggtg aagaccatcg gaggcgtgct cgccccagct 420 tgcagcgccc tgctgtgcga cttctaccgc atgcctagac aacagaaaaa ccagcagaag 480 gccgagctga agctgagcaa cgac 504 <210> 481 <211> 486 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50178" <400> 481 atgagcgcca tcgagctgaa ccacgagtac tggatgcggc acgccctggg cctggctcag 60 cgcgctagag atgagggcga ggtccccgtg ggcgccgtgc tggtctacca gaaccaggtg 120 atcggcgaag gatggaaccg ggccattggc ctgcatgacc ccacagccca cgccgaaatc 180 atggccctga gacagggcgg actggtgctg cagaattacc ggctgatcga caccaccctg 240 tacgtgacat tcgagccatg tgtgatgtgc gccggcgcta tggtgcactc tagaatcggt 300 agagtggtgt tcggcgttag aaacagcaag cggggcgccg ccggcagcct gatgaacgtg 360 ctcaattatc ctggcatgaa ccatagagtg gaagtgaccg agggcgtgct ggccggagaa 420 tgctccgcca tgctgtgcga cttctacaga gcccctaggg ctcaatttaa cgccccagaag 480 agacct 486 <210> 482 <211> 507 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50179" <400> 482 atgagcaacc ctgagctgaa ccacgagtac tggatgaggt acgccctgac cctggccaag 60 cgggccagag aggaaggcga agtgccagtg ggcgccgtgc tggttctgaa cgaacgggtg 120 atcggagaag gatggaacag agccatcggc ctgcatgacc ccaccgccca cgccgagatc 180 atggccctca gacagggcgg catggtcctg cagaactatc ggctgatcga caccaccctg 240 tacgtgacat ttgagccttg cgtgatgtgc gccggcgcta tggtgcactc tagaatcggc 300 cacctggtgt tcggcgtgcg gaacagcaag agaggagctg ctggttccct gatgaacgtg 360 ctgaattacc ccggcatgaa tcatagagtg gccattacag agggcgtgct gagagatgaa 420 tgtgccgcta tgctgtgcga cttctaccgc cagcctagac aagtgaagaa cgccctgaaa 480 aagaccctga gcgatagcca ggagcag 507 <210> 483 <211> 504 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50180" <400> 483 atgtccaatc ctgagcacga ccacgagtac tggatgcggc acgccctgaa cctggcccag 60 cgggccagag atgagggcga ggtgcccgtg ggcgccgtgc tggtgctcaa caaccaggtc 120 atcggagaag gctggaaccg cgccatcggc ctgcatgacc caacagccca tgctgaaatc 180 atggccctga gacagggcgg cctggtgctg cagaactacc ggctgctgga tacaaccctg 240 tacgtgacct tcgagccctg cgtgatgtgt agcggcgcta tggtgcacag ccggatcggc 300 accctggtct acggcgttag aaacgagaaa agaggcgccg ccggcagcct gatgaacgtg 360 ctgggatatc ctggaatgaa tcaccaggtg aacgtgatcg gcggagtgct ggctcaggac 420 tgttctgcca gactgtgcga cttctacaga atgcctagac agcaaaagaa ccagcagaga 480 gccgaactga aggcccaagg cgac 504 <210> 484 <211> 504 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50181" <400> 484 atgagcgacc ccgagctgaa tcacgagtat tggatgagac acgccctgca actggcccag 60 agagccagag atgagggcga agtgccagtg ggcgccgtgc tggtcctgaa caaccaggtg 120 attggagaag gctggaacag ggccatcgga ctgcatgatc ctacagccca cgccgaaatc 180 atggccctga gacagggcgg cctggtgctg cagaactacc ggctgctgga caccaccctg 240 tacgtgacct tcgagccttg cgtgatgtgc tctggcgcca tgatccacag cagaatcgga 300 acagtggtgt acggcgtgcg gaacgagaag cggggcgctg ctggcagcct gctgaatggtg 360 ctctcctacc ccggcatgaa ccaccaggtt aaggtgatcg gcgaagtgct ggcccctgct 420 tgtagcgcca tgctgtgcga cttctacaga atgcctagac agcagaaaaa ccagcaaaag 480 gccgagtgga agctgagcgg cgag 504 <210> 485 <211> 513 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized LPG50182" <400> 485 atgagcaacc ccgagctgaa ccacgagtac tggatgagat acgccctgac actggccaaa 60 agagccagag acgagggaga agtgcccgtg ggcgctgtgc tggtctacca cgaccaagtg 120 atcggcgaag gctggaacag agccatcgga ctgcatgatc ctaccgccca cgccgagatc 180 atggccctcc ggcagggagg cctggtgctg cagaactata gactgatcga caccacactg 240 tacgtgacct ttgagccttg tgtgatgtgc gccggcgcca tggtgcacag cagaattggc 300 agactggttt tcggcgtgcg caactctaag cggggcgccg ctggcagcct gctgaacgtg 360 ctgaattacc ctggcatgaa ccaccagatc gatatggaag aaggcgtgct gcgggatgag 420 tgcgccgcca tgctgtgcga cttctaccgg ctgcctagaa tcgtgaagaa tgcactgaag 480 cagtcccctc cagacagcac caacctgcat gcc 513 <210> 486 <211> 3213 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="Mammalian codon optimized nAPG07433.1" <400> 486 atgagagagc tggactacag aattggcctg gccatcggca ccaacagcat cggatggggc 60 gtgatcgagc tgtcctggaa caaagaccgg gagagatacg agaaggtcag aatcgtggat 120 caaggcgtga gaatgttcga cagagccgag atgcccaaga caggcgccag cttagctgaa 180 cccagaagaa tcgccagatc cagcagacgg agactgaatc gcaagtccca gagaaagaaa 240 aacatccgga acctgctggt gcaacacggc gtgatcacac aggaggaact ggatagcctg 300 taccccctga gcaaaaagag catggacatc tggggcattc ggctcgacgg cctggacaga 360 ctcctcaatc atttcgagtg ggccagactg ctgatccacc tggctcagag acggggcttt 420 aagtccaaca gaaagagtga actgaaagat acagagacag gcaaggtgct gagcagcatc 480 caactgaacg agaaacggct gagcttgtat agaaccgtgg gcgagatgtg gatgaaggac 540 cccgacttct ctaaatacga taggaagaga aatagcccca acgaatacgt gttcagcgtg 600 tctagagccg agctggaaaa ggaaatcgtg accctgttcg ccgcccagcg gagattccag 660 agcccttacg ccagcaaaga tctgcaggag acatatctgc agatctggac ccaccaactg 720 cctttcgcca gcggcaatgc catcctgaac aaggtcggat actgctccct gttgaaaggc 780 aaagaaagaa ggattcccaa ggctacatac accttccaat acttctctgc tctggaccag 840 gtgaatcgga ccagactggg acctgatttc cagcccttca ccaaggagca acgggaaatt 900 atcttgaaca acatgttcca gaggacagat tactacaaga agaaaaccat ccccgaggtg 960 acctactatg acatacggaa gtggctggaa ttggacgaga caattcagtt caagggcctg 1020 aactacgacc ctaacgagga actgaagaag atcgagaaga agccttttat caatctgaag 1080 gccttctacg agatcaacaa ggtggtggcc aactacagcg aaagaaccaa cgagaccttc 1140 tccaccctgg actacgacgg catcggctac gccctgaccg tgtacaaaac cgacaaggat 1200 atccgcagct acctgaagag cagtcacaac ctacctaaga gatgctacga cgaccaactg 1260 atcgaggaac tgctgagcct gagctacaca aagttcggcc acctgtccct gaaagccatc 1320 aaccacgtgc tgtctatcat gcagaagggc aatacctaca aggaagccgt ggaccaactg 1380 ggctacgaca ccagcggcct taagaaggag aagaggtcca agttcctgcc acctatttct 1440 gatgaaatca cgaatccaat cgtgaaaagg gccctgaccc aggccagaaa agtggtgaac 1500 gccataatta gaagacacgg atctcctcac tccgtgcaca tcgagctggc cagagagctg 1560 agcaagaacc acgacgagcg gacaaagatc gtcagcgccc aggatgaaaa ctacaagaaa 1620 aacaagggcg ctatcagcat cctgtctgag cacggcatcc tgaaccctac aggctacgac 1680 atcgtgagat acaaactgtg gaaggagcag ggcgaacggt gcgcctacag cctgaaggaa 1740 atccctgccg atacattttt caacgagctg aagaaggaac gcaacggcgc ccctatcctt 1800 gaagtggacc acatcctgcc ctacagccag tccttcatcg actcctacca caacaaggtc 1860 ctggtgtaca gcgacgaaaa ccggaaaaag ggcaacagaa tcccttatac ctacttcctg 1920 gaaaccaaca aggattggga ggcctttgag cggtacgtgc ggagcaacaa attcttctcc 1980 aagaaaaagc gagagtacct tctgaagcgg gcttatctgc ctagagaatc tgagctgatc 2040 aaagaacgcc acctgaacga caccagatac gcctctacct tcctgaagaa cttcatcgag 2100 cagaacctgc agttcaagga agccgaggac aaccccagaa aaagacgggt gcaaaccgtg 2160 aacggcgtta tcaccgccca cttcagaaag cggtggggcc tggagaagga ccggcaggag 2220 acatacctcc atcacgctat ggacgccatc atcgtggctt gtacagacca ccacatggtc 2280 accagagtga ccgagtacta tcagatcaag gaaagcaaca agagcgtgaa gaagccctat 2340 tttcctatgc cttgggaagg cttccgggac gagctgctga gccacttggc ttctcagcct 2400 atcgccaaga aaatcagcga ggaactgaag gccggctacc agagcctgga ctacatcttc 2460 gtgtccagaa tgcctaagag aagcattaca ggcgctgctc ataagcagac catcatgcgg 2520 aagggaggaa ttgacaagaa gggcaaaaca atcatcatcg aacggctgca cctgaaggat 2580 atcaagttcg acgagaacgg agatttcaag atggtgggca aggaacagga catggccaca 2640 tacgaagcta ttaaacagag atacctggag cacggcaaga atagcaagaa ggccttcgag 2700 acccctctgt acaagcccag caaaaagggc acaggtaacc tgatcaagcg ggtgaaggtg 2760 gaaggacagg ccaagagctt tgtgagggaa gtgaacggcg gagtggccca aaatggcgat 2820 ctggttagag ttgatttgtt tgagaaggat gataagtact acatggtccc catctacgtg 2880 ccagacaccg tgtgtagcga gctgcccaaa aaggtggtcg ccagctctaa gggctatgag 2940 cagtggctga cactggataa cagcttcacc tttaagttca gcctgtaccc ttatgatctg 3000 gtgcggctgg tcaagggaga tgaggatcgg ttcctgtact ttggcaccct ggacatcgac 3060 agcgacagac ttaacttcaa ggacgtgaac aagccaagca agaagaacga gtaccggtac 3120 agcttgaaaa ccatcgagga cttggagaag tacgaggtgg gcgtgctggg cgatctaaga 3180 ctggtccgga aggaaactcg aagaaacttc cac 3213 <210> 487 <211> 96 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="Codon optimized linker" <400> 487 tccggcgggt cttccggcgg ctctagtggg agtgagacgc caggaacgtc tgaatctgct 60 actcccgaat ctagcggcgg atccagtggc ggtagt 96 <210> 488 <211> 1323 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50140-nAPG07433.1 protein sequence" <400> 488 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp Leu Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu Gln 35 40 45 Leu Ala Lys Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Thr Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His Gln 145 150 155 160 Val Gln Ile Ile Asp Gly Val Leu Ala Pro Glu Cys Ser Gly Leu Leu 165 170 175 Cys Asp Phe Tyr Arg Met Pro Arg Gln Val Phe Asn Gln Gln Lys Ala 180 185 190 Glu Ser Thr Ser Ile Asn Gly Asp Ser Gly Gly Ser Ser Gly Gly Ser 195 200 205 Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser 210 215 220 Ser Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile 225 230 235 240 Gly Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu 245 250 255 Ser Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp 260 265 270 Gln Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala 275 280 285 Ser Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu 290 295 300 Asn Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln 305 310 315 320 His Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser 325 330 335 Lys Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg 340 345 350 Leu Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln 355 360 365 Arg Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu 370 375 380 Thr Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser 385 390 395 400 Leu Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser 405 410 415 Lys Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val 420 425 430 Ser Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln 435 440 445 Arg Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr 450 455 460 Leu Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile 465 470 475 480 Leu Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg 485 490 495 Ile Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln 500 505 510 Val Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu 515 520 525 Gln Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr 530 535 540 Lys Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp 545 550 555 560 Leu Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro 565 570 575 Asn Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys 580 585 590 Ala Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr 595 600 605 Asn Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu 610 615 620 Thr Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser 625 630 635 640 His Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu 645 650 655 Leu Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile 660 665 670 Asn His Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala 675 680 685 Val Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg 690 695 700 Ser Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val 705 710 715 720 Lys Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg 725 730 735 Arg His Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu 740 745 750 Ser Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu 755 760 765 Asn Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly 770 775 780 Ile Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys 785 790 795 800 Glu Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp 805 810 815 Thr Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu 820 825 830 Glu Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr 835 840 845 His Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn 850 855 860 Arg Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala 865 870 875 880 Phe Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg 885 890 895 Glu Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile 900 905 910 Lys Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys 915 920 925 Asn Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro 930 935 940 Arg Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe 945 950 955 960 Arg Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His 965 970 975 His Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val 980 985 990 Thr Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val 995 1000 1005 Lys Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu 1010 1015 1020 Leu Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser 1025 1030 1035 Glu Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val 1040 1045 1050 Ser Arg Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln 1055 1060 1065 Thr Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile 1070 1075 1080 Ile Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn 1085 1090 1095 Gly Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr 1100 1105 1110 Glu Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys 1115 1120 1125 Lys Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr 1130 1135 1140 Gly Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser 1145 1150 1155 Phe Val Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu 1160 1165 1170 Val Arg Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val 1175 1180 1185 Pro Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys 1190 1195 1200 Val Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp 1205 1210 1215 Asn Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val 1220 1225 1230 Arg Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr 1235 1240 1245 Leu Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys 1250 1255 1260 Pro Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu 1265 1270 1275 Asp Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu 1280 1285 1290 Val Arg Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys 1295 1300 1305 Arg Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 489 <211> 1318 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50141-nAPG07433.1 protein sequence" <400> 489 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asn Pro Glu Leu Thr His Glu His Trp Met Arg Tyr Ala Leu Thr 35 40 45 Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Gln Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Ile Glu Phe Thr Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg Gln Pro Arg Gln Val Phe Asn Ala Leu Lys Thr 180 185 190 Gly Asn Ala Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Ser Glu Thr 195 200 205 Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser Gly Gly Ser Ser 210 215 220 Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu Ala Ile Gly 225 230 235 240 Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser Trp Asn Lys Asp 245 250 255 Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln Gly Val Arg Met 260 265 270 Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser Leu Ala Glu Pro 275 280 285 Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys Ser Gln 290 295 300 Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His Gly Val Ile Thr 305 310 315 320 Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys Ser Met Asp 325 330 335 Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn His Phe 340 345 350 Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly Phe Lys 355 360 365 Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly Lys Val Leu 370 375 380 Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr Arg Thr Val 385 390 395 400 Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr Asp Arg Lys 405 410 415 Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala Glu Leu 420 425 430 Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg Arg Phe Gln Ser 435 440 445 Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln Ile Trp Thr 450 455 460 His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys Val Gly 465 470 475 480 Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys Ala Thr 485 490 495 Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg Thr Arg 500 505 510 Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg Glu Ile Ile 515 520 525 Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys Thr Ile 530 535 540 Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu Asp Glu 545 550 555 560 Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu Leu Lys 565 570 575 Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr Glu Ile 580 585 590 Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu Thr Phe Ser 595 600 605 Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val Tyr Lys Thr 610 615 620 Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His Asn Leu Pro Lys 625 630 635 640 Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser Leu Ser Tyr 645 650 655 Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn His Val Leu Ser 660 665 670 Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp Gln Leu Gly 675 680 685 Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys Phe Leu Pro 690 695 700 Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala Leu Thr 705 710 715 720 Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg His Gly Ser Pro 725 730 735 His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser Lys Asn His Asp 740 745 750 Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr Lys Lys Asn 755 760 765 Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile Leu Asn Pro Thr 770 775 780 Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly Glu Arg 785 790 795 800 Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe Phe Asn Glu 805 810 815 Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu Val Asp His Ile 820 825 830 Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His Asn Lys Val Leu 835 840 845 Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg Ile Pro Tyr Thr 850 855 860 Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu Arg Tyr Val 865 870 875 880 Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu Tyr Leu Leu Lys 885 890 895 Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu Arg His Leu 900 905 910 Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe Ile Glu Gln 915 920 925 Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg Lys Arg Arg Val 930 935 940 Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg Lys Arg Trp Gly 945 950 955 960 Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His Ala Met Asp Ala 965 970 975 Ile Ile Val Ala Cys Thr Asp His His Met Val Thr Arg Val Thr Glu 980 985 990 Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys Lys Pro Tyr Phe 995 1000 1005 Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu Leu Ser His Leu 1010 1015 1020 Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu Leu Lys Ala 1025 1030 1035 Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser Arg Met Pro Lys 1040 1045 1050 Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr Ile Met Arg Lys 1055 1060 1065 Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile Glu Arg Leu 1070 1075 1080 His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp Phe Lys Met 1085 1090 1095 Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu Ala Ile Lys Gln 1100 1105 1110 Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys Ala Phe Glu Thr 1115 1120 1125 Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly Asn Leu Ile Lys 1130 1135 1140 Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe Val Arg Glu Val 1145 1150 1155 Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val Arg Val Asp Leu 1160 1165 1170 Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile Tyr Val Pro 1175 1180 1185 Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val Val Ala Ser Ser 1190 1195 1200 Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser Phe Thr Phe 1205 1210 1215 Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu Val Lys Gly 1220 1225 1230 Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp Ile Asp Ser 1235 1240 1245 Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro Ser Lys Lys Asn 1250 1255 1260 Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp Leu Glu Lys Tyr 1265 1270 1275 Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val Arg Lys Glu Thr 1280 1285 1290 Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg Pro Ala Ala Thr 1295 1300 1305 Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 <210> 490 <211> 1323 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50142-nAPG07433.1 protein sequence" <400> 490 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Ile Pro Glu Leu Asn His Asp Val Trp Met Arg His Ala Leu Thr 35 40 45 Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Gly Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Gln Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Val Ala Ile Thr Glu Gly Val Leu Arg Glu Glu Cys Ala Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg Gln Pro Arg Gln Val Phe Asn Ala Leu Lys Lys 180 185 190 Pro Ala Gly Asp Ile Asn Ala Phe Ser Gly Gly Ser Ser Gly Gly Ser 195 200 205 Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser 210 215 220 Ser Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile 225 230 235 240 Gly Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu 245 250 255 Ser Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp 260 265 270 Gln Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala 275 280 285 Ser Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu 290 295 300 Asn Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln 305 310 315 320 His Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser 325 330 335 Lys Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg 340 345 350 Leu Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln 355 360 365 Arg Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu 370 375 380 Thr Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser 385 390 395 400 Leu Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser 405 410 415 Lys Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val 420 425 430 Ser Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln 435 440 445 Arg Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr 450 455 460 Leu Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile 465 470 475 480 Leu Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg 485 490 495 Ile Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln 500 505 510 Val Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu 515 520 525 Gln Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr 530 535 540 Lys Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp 545 550 555 560 Leu Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro 565 570 575 Asn Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys 580 585 590 Ala Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr 595 600 605 Asn Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu 610 615 620 Thr Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser 625 630 635 640 His Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu 645 650 655 Leu Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile 660 665 670 Asn His Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala 675 680 685 Val Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg 690 695 700 Ser Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val 705 710 715 720 Lys Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg 725 730 735 Arg His Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu 740 745 750 Ser Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu 755 760 765 Asn Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly 770 775 780 Ile Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys 785 790 795 800 Glu Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp 805 810 815 Thr Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu 820 825 830 Glu Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr 835 840 845 His Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn 850 855 860 Arg Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala 865 870 875 880 Phe Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg 885 890 895 Glu Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile 900 905 910 Lys Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys 915 920 925 Asn Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro 930 935 940 Arg Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe 945 950 955 960 Arg Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His 965 970 975 His Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val 980 985 990 Thr Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val 995 1000 1005 Lys Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu 1010 1015 1020 Leu Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser 1025 1030 1035 Glu Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val 1040 1045 1050 Ser Arg Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln 1055 1060 1065 Thr Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile 1070 1075 1080 Ile Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn 1085 1090 1095 Gly Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr 1100 1105 1110 Glu Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys 1115 1120 1125 Lys Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr 1130 1135 1140 Gly Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser 1145 1150 1155 Phe Val Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu 1160 1165 1170 Val Arg Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val 1175 1180 1185 Pro Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys 1190 1195 1200 Val Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp 1205 1210 1215 Asn Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val 1220 1225 1230 Arg Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr 1235 1240 1245 Leu Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys 1250 1255 1260 Pro Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu 1265 1270 1275 Asp Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu 1280 1285 1290 Val Arg Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys 1295 1300 1305 Arg Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 491 <211> 1326 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50143-nAPG07433.1 protein sequence" <400> 491 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asn Pro Glu Leu Asn His Glu Tyr Trp Met Arg Tyr Ala Leu Thr 35 40 45 Leu Ala Lys Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asp Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Arg Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Leu Asn Val Leu Asn Tyr Pro Gly Met Asn His His 145 150 155 160 Ile Glu Met Glu Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg Gln Pro Arg Gln Val Phe Asn Ala Leu Lys Lys 180 185 190 Ser Pro Pro Asp Ile Asn Asn Leu Gln Ala Arg Ser Gly Gly Ser Ser 195 200 205 Gly Gly Ser Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr 210 215 220 Pro Glu Ser Ser Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp 225 230 235 240 Tyr Arg Ile Gly Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val 245 250 255 Ile Glu Leu Ser Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg 260 265 270 Ile Val Asp Gln Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys 275 280 285 Thr Gly Ala Ser Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg 290 295 300 Arg Arg Leu Asn Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu 305 310 315 320 Leu Val Gln His Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr 325 330 335 Pro Leu Ser Lys Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly 340 345 350 Leu Asp Arg Leu Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile His 355 360 365 Leu Ala Gln Arg Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys 370 375 380 Asp Thr Glu Thr Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys 385 390 395 400 Arg Leu Ser Leu Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro 405 410 415 Asp Phe Ser Lys Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val 420 425 430 Phe Ser Val Ser Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe 435 440 445 Ala Ala Gln Arg Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln 450 455 460 Glu Thr Tyr Leu Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly 465 470 475 480 Asn Ala Ile Leu Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys 485 490 495 Glu Arg Arg Ile Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala 500 505 510 Leu Asp Gln Val Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe 515 520 525 Thr Lys Glu Gln Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr 530 535 540 Asp Tyr Tyr Lys Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile 545 550 555 560 Arg Lys Trp Leu Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn 565 570 575 Tyr Asp Pro Asn Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile 580 585 590 Asn Leu Lys Ala Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser 595 600 605 Glu Arg Thr Asn Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly 610 615 620 Tyr Ala Leu Thr Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu 625 630 635 640 Lys Ser Ser His Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile 645 650 655 Glu Glu Leu Leu Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu 660 665 670 Lys Ala Ile Asn His Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr 675 680 685 Lys Glu Ala Val Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys 690 695 700 Glu Lys Arg Ser Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn 705 710 715 720 Pro Ile Val Lys Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala 725 730 735 Ile Ile Arg Arg His Gly Ser Pro His Ser Val His Ile Glu Leu Ala 740 745 750 Arg Glu Leu Ser Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala 755 760 765 Gln Asp Glu Asn Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser 770 775 780 Glu His Gly Ile Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys 785 790 795 800 Leu Trp Lys Glu Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile 805 810 815 Pro Ala Asp Thr Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala 820 825 830 Pro Ile Leu Glu Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile 835 840 845 Asp Ser Tyr His Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys 850 855 860 Lys Gly Asn Arg Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp 865 870 875 880 Trp Glu Ala Phe Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys 885 890 895 Lys Lys Arg Glu Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser 900 905 910 Glu Leu Ile Lys Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr 915 920 925 Phe Leu Lys Asn Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu 930 935 940 Asp Asn Pro Arg Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr 945 950 955 960 Ala His Phe Arg Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr 965 970 975 Tyr Leu His His Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His 980 985 990 His Met Val Thr Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn 995 1000 1005 Lys Ser Val Lys Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe 1010 1015 1020 Arg Asp Glu Leu Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys 1025 1030 1035 Lys Ile Ser Glu Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr 1040 1045 1050 Ile Phe Val Ser Arg Met Pro Lys Arg Ser Ile Thr Gly Ala Ala 1055 1060 1065 His Lys Gln Thr Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly 1070 1075 1080 Lys Thr Ile Ile Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe 1085 1090 1095 Asp Glu Asn Gly Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met 1100 1105 1110 Ala Thr Tyr Glu Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys 1115 1120 1125 Asn Ser Lys Lys Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys 1130 1135 1140 Lys Gly Thr Gly Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln 1145 1150 1155 Ala Lys Ser Phe Val Arg Glu Val Asn Gly Gly Val Ala Gln Asn 1160 1165 1170 Gly Asp Leu Val Arg Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr 1175 1180 1185 Tyr Met Val Pro Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu 1190 1195 1200 Pro Lys Lys Val Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu 1205 1210 1215 Thr Leu Asp Asn Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr 1220 1225 1230 Asp Leu Val Arg Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr 1235 1240 1245 Phe Gly Thr Leu Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp 1250 1255 1260 Val Asn Lys Pro Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys 1265 1270 1275 Thr Ile Glu Asp Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp 1280 1285 1290 Leu Arg Leu Val Arg Lys Glu Thr Arg Arg Asn Phe His Ser Gly 1295 1300 1305 Gly Ser Lys Arg Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys 1310 1315 1320 Lys Lys Lys 1325 <210> 492 <211> 1323 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50144-nAPG07433.1 protein sequence" <400> 492 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asn Pro Glu Leu Thr His Asp His Trp Met Arg His Ala Leu Thr 35 40 45 Leu Ala Gln Arg Ala Arg Asn Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Gly Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Val Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Gln Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Val Glu Ile Ile Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg His Pro Arg Gln Val Phe Asn Ala Leu Lys Lys 180 185 190 Asn Ala Gly Thr Ile Asn Thr Gln Ser Gly Gly Ser Ser Gly Gly Ser 195 200 205 Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser 210 215 220 Ser Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile 225 230 235 240 Gly Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu 245 250 255 Ser Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp 260 265 270 Gln Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala 275 280 285 Ser Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu 290 295 300 Asn Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln 305 310 315 320 His Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser 325 330 335 Lys Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg 340 345 350 Leu Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln 355 360 365 Arg Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu 370 375 380 Thr Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser 385 390 395 400 Leu Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser 405 410 415 Lys Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val 420 425 430 Ser Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln 435 440 445 Arg Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr 450 455 460 Leu Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile 465 470 475 480 Leu Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg 485 490 495 Ile Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln 500 505 510 Val Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu 515 520 525 Gln Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr 530 535 540 Lys Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp 545 550 555 560 Leu Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro 565 570 575 Asn Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys 580 585 590 Ala Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr 595 600 605 Asn Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu 610 615 620 Thr Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser 625 630 635 640 His Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu 645 650 655 Leu Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile 660 665 670 Asn His Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala 675 680 685 Val Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg 690 695 700 Ser Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val 705 710 715 720 Lys Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg 725 730 735 Arg His Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu 740 745 750 Ser Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu 755 760 765 Asn Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly 770 775 780 Ile Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys 785 790 795 800 Glu Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp 805 810 815 Thr Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu 820 825 830 Glu Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr 835 840 845 His Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn 850 855 860 Arg Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala 865 870 875 880 Phe Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg 885 890 895 Glu Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile 900 905 910 Lys Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys 915 920 925 Asn Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro 930 935 940 Arg Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe 945 950 955 960 Arg Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His 965 970 975 His Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val 980 985 990 Thr Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val 995 1000 1005 Lys Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu 1010 1015 1020 Leu Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser 1025 1030 1035 Glu Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val 1040 1045 1050 Ser Arg Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln 1055 1060 1065 Thr Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile 1070 1075 1080 Ile Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn 1085 1090 1095 Gly Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr 1100 1105 1110 Glu Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys 1115 1120 1125 Lys Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr 1130 1135 1140 Gly Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser 1145 1150 1155 Phe Val Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu 1160 1165 1170 Val Arg Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val 1175 1180 1185 Pro Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys 1190 1195 1200 Val Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp 1205 1210 1215 Asn Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val 1220 1225 1230 Arg Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr 1235 1240 1245 Leu Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys 1250 1255 1260 Pro Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu 1265 1270 1275 Asp Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu 1280 1285 1290 Val Arg Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys 1295 1300 1305 Arg Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 493 <211> 1320 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50145-nAPG07433.1 protein sequence" <400> 493 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp Thr Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu Met 35 40 45 Leu Ala Lys Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Lys Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Asn Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Val Glu Ile Ala Glu Gly Val Leu Ala Asp Glu Cys Ser Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg His Pro Arg Gln Val Phe Asn Ala Leu Lys Gln 180 185 190 Ala Ala Lys His Ile Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Ser 195 200 205 Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser Gly Gly 210 215 220 Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu Ala 225 230 235 240 Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser Trp Asn 245 250 255 Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln Gly Val 260 265 270 Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser Leu Ala 275 280 285 Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys 290 295 300 Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His Gly Val 305 310 315 320 Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys Ser 325 330 335 Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn 340 345 350 His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly 355 360 365 Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly Lys 370 375 380 Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr Arg 385 390 395 400 Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr Asp 405 410 415 Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala 420 425 430 Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg Arg Phe 435 440 445 Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln Ile 450 455 460 Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys 465 470 475 480 Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys 485 490 495 Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg 500 505 510 Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg Glu 515 520 525 Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys 530 535 540 Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu 545 550 555 560 Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu 565 570 575 Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr 580 585 590 Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu Thr 595 600 605 Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val Tyr 610 615 620 Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His Asn Leu 625 630 635 640 Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser Leu 645 650 655 Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn His Val 660 665 670 Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp Gln 675 680 685 Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys Phe 690 695 700 Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala 705 710 715 720 Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg His Gly 725 730 735 Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser Lys Asn 740 745 750 His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr Lys 755 760 765 Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile Leu Asn 770 775 780 Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly 785 790 795 800 Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe Phe 805 810 815 Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu Val Asp 820 825 830 His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His Asn Lys 835 840 845 Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg Ile Pro 850 855 860 Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu Arg 865 870 875 880 Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu Tyr Leu 885 890 895 Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu Arg 900 905 910 His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe Ile 915 920 925 Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg Lys Arg 930 935 940 Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg Lys Arg 945 950 955 960 Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His Ala Met 965 970 975 Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val Thr Arg Val 980 985 990 Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys Lys Pro 995 1000 1005 Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu Leu Ser 1010 1015 1020 His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu Leu 1025 1030 1035 Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser Arg Met 1040 1045 1050 Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr Ile Met 1055 1060 1065 Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile Glu 1070 1075 1080 Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp Phe 1085 1090 1095 Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu Ala Ile 1100 1105 1110 Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys Ala Phe 1115 1120 1125 Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly Asn Leu 1130 1135 1140 Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe Val Arg 1145 1150 1155 Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val Arg Val 1160 1165 1170 Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile Tyr 1175 1180 1185 Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val Val Ala 1190 1195 1200 Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser Phe 1205 1210 1215 Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu Val 1220 1225 1230 Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp Ile 1235 1240 1245 Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro Ser Lys 1250 1255 1260 Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp Leu Glu 1265 1270 1275 Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val Arg Lys 1280 1285 1290 Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg Pro Ala 1295 1300 1305 Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 494 <211> 1325 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50146-nAPG07433.1 protein sequence" <400> 494 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp Ile Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu Met 35 40 45 Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly His Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Ile Glu Phe Thr Glu Gly Val Leu Ala Asp Glu Cys Ser Gly Met Leu 165 170 175 Cys Asp Phe Tyr Arg Tyr Pro Arg Gln Val Phe Asn Thr Leu Lys Gln 180 185 190 Ala Ala Lys Ala Ile Asn Pro Ala Ala Gln Ser Gly Gly Ser Ser Gly 195 200 205 Gly Ser Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro 210 215 220 Glu Ser Ser Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr 225 230 235 240 Arg Ile Gly Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile 245 250 255 Glu Leu Ser Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile 260 265 270 Val Asp Gln Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr 275 280 285 Gly Ala Ser Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg 290 295 300 Arg Leu Asn Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu 305 310 315 320 Val Gln His Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro 325 330 335 Leu Ser Lys Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu 340 345 350 Asp Arg Leu Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu 355 360 365 Ala Gln Arg Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp 370 375 380 Thr Glu Thr Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg 385 390 395 400 Leu Ser Leu Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp 405 410 415 Phe Ser Lys Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe 420 425 430 Ser Val Ser Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala 435 440 445 Ala Gln Arg Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu 450 455 460 Thr Tyr Leu Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn 465 470 475 480 Ala Ile Leu Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu 485 490 495 Arg Arg Ile Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu 500 505 510 Asp Gln Val Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr 515 520 525 Lys Glu Gln Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp 530 535 540 Tyr Tyr Lys Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg 545 550 555 560 Lys Trp Leu Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr 565 570 575 Asp Pro Asn Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn 580 585 590 Leu Lys Ala Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu 595 600 605 Arg Thr Asn Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr 610 615 620 Ala Leu Thr Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys 625 630 635 640 Ser Ser His Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu 645 650 655 Glu Leu Leu Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys 660 665 670 Ala Ile Asn His Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys 675 680 685 Glu Ala Val Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu 690 695 700 Lys Arg Ser Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro 705 710 715 720 Ile Val Lys Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile 725 730 735 Ile Arg Arg His Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg 740 745 750 Glu Leu Ser Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln 755 760 765 Asp Glu Asn Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu 770 775 780 His Gly Ile Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu 785 790 795 800 Trp Lys Glu Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro 805 810 815 Ala Asp Thr Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro 820 825 830 Ile Leu Glu Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp 835 840 845 Ser Tyr His Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys 850 855 860 Gly Asn Arg Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp 865 870 875 880 Glu Ala Phe Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys 885 890 895 Lys Arg Glu Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu 900 905 910 Leu Ile Lys Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe 915 920 925 Leu Lys Asn Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp 930 935 940 Asn Pro Arg Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala 945 950 955 960 His Phe Arg Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr 965 970 975 Leu His His Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His 980 985 990 Met Val Thr Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys 995 1000 1005 Ser Val Lys Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg 1010 1015 1020 Asp Glu Leu Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys 1025 1030 1035 Ile Ser Glu Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile 1040 1045 1050 Phe Val Ser Arg Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His 1055 1060 1065 Lys Gln Thr Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys 1070 1075 1080 Thr Ile Ile Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp 1085 1090 1095 Glu Asn Gly Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala 1100 1105 1110 Thr Tyr Glu Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn 1115 1120 1125 Ser Lys Lys Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys 1130 1135 1140 Gly Thr Gly Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala 1145 1150 1155 Lys Ser Phe Val Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly 1160 1165 1170 Asp Leu Val Arg Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr 1175 1180 1185 Met Val Pro Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro 1190 1195 1200 Lys Lys Val Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr 1205 1210 1215 Leu Asp Asn Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp 1220 1225 1230 Leu Val Arg Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe 1235 1240 1245 Gly Thr Leu Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val 1250 1255 1260 Asn Lys Pro Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr 1265 1270 1275 Ile Glu Asp Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu 1280 1285 1290 Arg Leu Val Arg Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly 1295 1300 1305 Ser Lys Arg Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys 1310 1315 1320 Lys Lys 1325 <210> 495 <211> 1327 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50147-nAPG07433.1 protein sequence" <400> 495 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Ile Pro Glu Leu Asn His Asp Val Trp Met Arg His Ala Leu Thr 35 40 45 Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Gly Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Gln Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Val Glu Ile Thr Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg Gln Pro Arg Gln Val Phe Asn Ala Leu Lys Lys 180 185 190 Pro Ala Gly Asp Ile Asn Ala Leu Gln Asn Asn Arg Ser Gly Gly Ser 195 200 205 Ser Gly Gly Ser Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala 210 215 220 Thr Pro Glu Ser Ser Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu 225 230 235 240 Asp Tyr Arg Ile Gly Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly 245 250 255 Val Ile Glu Leu Ser Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val 260 265 270 Arg Ile Val Asp Gln Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro 275 280 285 Lys Thr Gly Ala Ser Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser 290 295 300 Arg Arg Arg Leu Asn Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn 305 310 315 320 Leu Leu Val Gln His Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu 325 330 335 Tyr Pro Leu Ser Lys Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp 340 345 350 Gly Leu Asp Arg Leu Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile 355 360 365 His Leu Ala Gln Arg Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu 370 375 380 Lys Asp Thr Glu Thr Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu 385 390 395 400 Lys Arg Leu Ser Leu Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp 405 410 415 Pro Asp Phe Ser Lys Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr 420 425 430 Val Phe Ser Val Ser Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu 435 440 445 Phe Ala Ala Gln Arg Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu 450 455 460 Gln Glu Thr Tyr Leu Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser 465 470 475 480 Gly Asn Ala Ile Leu Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly 485 490 495 Lys Glu Arg Arg Ile Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser 500 505 510 Ala Leu Asp Gln Val Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro 515 520 525 Phe Thr Lys Glu Gln Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg 530 535 540 Thr Asp Tyr Tyr Lys Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp 545 550 555 560 Ile Arg Lys Trp Leu Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu 565 570 575 Asn Tyr Asp Pro Asn Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe 580 585 590 Ile Asn Leu Lys Ala Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr 595 600 605 Ser Glu Arg Thr Asn Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile 610 615 620 Gly Tyr Ala Leu Thr Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr 625 630 635 640 Leu Lys Ser Ser His Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu 645 650 655 Ile Glu Glu Leu Leu Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser 660 665 670 Leu Lys Ala Ile Asn His Val Leu Ser Ile Met Gln Lys Gly Asn Thr 675 680 685 Tyr Lys Glu Ala Val Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys 690 695 700 Lys Glu Lys Arg Ser Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr 705 710 715 720 Asn Pro Ile Val Lys Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn 725 730 735 Ala Ile Ile Arg Arg His Gly Ser Pro His Ser Val His Ile Glu Leu 740 745 750 Ala Arg Glu Leu Ser Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser 755 760 765 Ala Gln Asp Glu Asn Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu 770 775 780 Ser Glu His Gly Ile Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr 785 790 795 800 Lys Leu Trp Lys Glu Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu 805 810 815 Ile Pro Ala Asp Thr Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly 820 825 830 Ala Pro Ile Leu Glu Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe 835 840 845 Ile Asp Ser Tyr His Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg 850 855 860 Lys Lys Gly Asn Arg Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys 865 870 875 880 Asp Trp Glu Ala Phe Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser 885 890 895 Lys Lys Lys Arg Glu Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu 900 905 910 Ser Glu Leu Ile Lys Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser 915 920 925 Thr Phe Leu Lys Asn Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala 930 935 940 Glu Asp Asn Pro Arg Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile 945 950 955 960 Thr Ala His Phe Arg Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu 965 970 975 Thr Tyr Leu His His Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp 980 985 990 His His Met Val Thr Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser 995 1000 1005 Asn Lys Ser Val Lys Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly 1010 1015 1020 Phe Arg Asp Glu Leu Leu Ser His Leu Ala Ser Gln Pro Ile Ala 1025 1030 1035 Lys Lys Ile Ser Glu Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp 1040 1045 1050 Tyr Ile Phe Val Ser Arg Met Pro Lys Arg Ser Ile Thr Gly Ala 1055 1060 1065 Ala His Lys Gln Thr Ile Met Arg Lys Gly Gly Ile Asp Lys Lys 1070 1075 1080 Gly Lys Thr Ile Ile Ile Glu Arg Leu His Leu Lys Asp Ile Lys 1085 1090 1095 Phe Asp Glu Asn Gly Asp Phe Lys Met Val Gly Lys Glu Gln Asp 1100 1105 1110 Met Ala Thr Tyr Glu Ala Ile Lys Gln Arg Tyr Leu Glu His Gly 1115 1120 1125 Lys Asn Ser Lys Lys Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser 1130 1135 1140 Lys Lys Gly Thr Gly Asn Leu Ile Lys Arg Val Lys Val Glu Gly 1145 1150 1155 Gln Ala Lys Ser Phe Val Arg Glu Val Asn Gly Gly Val Ala Gln 1160 1165 1170 Asn Gly Asp Leu Val Arg Val Asp Leu Phe Glu Lys Asp Asp Lys 1175 1180 1185 Tyr Tyr Met Val Pro Ile Tyr Val Pro Asp Thr Val Cys Ser Glu 1190 1195 1200 Leu Pro Lys Lys Val Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp 1205 1210 1215 Leu Thr Leu Asp Asn Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro 1220 1225 1230 Tyr Asp Leu Val Arg Leu Val Lys Gly Asp Glu Asp Arg Phe Leu 1235 1240 1245 Tyr Phe Gly Thr Leu Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys 1250 1255 1260 Asp Val Asn Lys Pro Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu 1265 1270 1275 Lys Thr Ile Glu Asp Leu Glu Lys Tyr Glu Val Gly Val Leu Gly 1280 1285 1290 Asp Leu Arg Leu Val Arg Lys Glu Thr Arg Arg Asn Phe His Ser 1295 1300 1305 Gly Gly Ser Lys Arg Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala 1310 1315 1320 Lys Lys Lys Lys 1325 <210> 496 <211> 1322 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50148-nAPG07433.1 protein sequence" <400> 496 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asn Pro Glu Phe Thr His Glu Tyr Trp Met Arg His Ala Leu Thr 35 40 45 Leu Ala Arg Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Thr Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His Gln 145 150 155 160 Val Lys Thr Ile Gly Gly Val Leu Ala Pro Glu Cys Ser Gly Leu Leu 165 170 175 Cys Asp Phe Tyr Arg Met Pro Arg Gln Val Phe Asn Gln Gln Lys Ala 180 185 190 Glu Leu Lys Ser Ile Asn Asp Ser Gly Gly Ser Ser Gly Gly Ser Ser 195 200 205 Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser 210 215 220 Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly 225 230 235 240 Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser 245 250 255 Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln 260 265 270 Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser 275 280 285 Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn 290 295 300 Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His 305 310 315 320 Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys 325 330 335 Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu 340 345 350 Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg 355 360 365 Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr 370 375 380 Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu 385 390 395 400 Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys 405 410 415 Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser 420 425 430 Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg 435 440 445 Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu 450 455 460 Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu 465 470 475 480 Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile 485 490 495 Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val 500 505 510 Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln 515 520 525 Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys 530 535 540 Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu 545 550 555 560 Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn 565 570 575 Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala 580 585 590 Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn 595 600 605 Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr 610 615 620 Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His 625 630 635 640 Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu 645 650 655 Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn 660 665 670 His Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val 675 680 685 Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser 690 695 700 Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys 705 710 715 720 Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg 725 730 735 His Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser 740 745 750 Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn 755 760 765 Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile 770 775 780 Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu 785 790 795 800 Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr 805 810 815 Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu 820 825 830 Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His 835 840 845 Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg 850 855 860 Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe 865 870 875 880 Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu 885 890 895 Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys 900 905 910 Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn 915 920 925 Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg 930 935 940 Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg 945 950 955 960 Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His 965 970 975 Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val Thr 980 985 990 Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys 995 1000 1005 Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu 1010 1015 1020 Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu 1025 1030 1035 Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser 1040 1045 1050 Arg Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr 1055 1060 1065 Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile 1070 1075 1080 Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly 1085 1090 1095 Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu 1100 1105 1110 Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys 1115 1120 1125 Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly 1130 1135 1140 Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe 1145 1150 1155 Val Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val 1160 1165 1170 Arg Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro 1175 1180 1185 Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val 1190 1195 1200 Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn 1205 1210 1215 Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg 1220 1225 1230 Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu 1235 1240 1245 Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro 1250 1255 1260 Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp 1265 1270 1275 Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val 1280 1285 1290 Arg Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg 1295 1300 1305 Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 497 <211> 1321 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50149-nAPG07433.1 protein sequence" <400> 497 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp Ala Glu Leu Thr His Glu Tyr Trp Met Arg His Ala Leu Thr 35 40 45 Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Gln Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Arg Leu Ile Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Val Glu Val Val Glu Gly Ile Leu Arg Asp Glu Cys Ala Gly Met Leu 165 170 175 Cys Asp Phe Tyr Arg Gln Pro Arg Gln Val Phe Asn Ala Leu Lys Lys 180 185 190 Gly Ala Thr Asp Ile Asn Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly 195 200 205 Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser Gly 210 215 220 Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu 225 230 235 240 Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser Trp 245 250 255 Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln Gly 260 265 270 Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser Leu 275 280 285 Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg 290 295 300 Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His Gly 305 310 315 320 Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys 325 330 335 Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu 340 345 350 Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg Arg 355 360 365 Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly 370 375 380 Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr 385 390 395 400 Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr 405 410 415 Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser Arg 420 425 430 Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg Arg 435 440 445 Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln 450 455 460 Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn 465 470 475 480 Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro 485 490 495 Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn 500 505 510 Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg 515 520 525 Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys 530 535 540 Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu 545 550 555 560 Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu 565 570 575 Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe 580 585 590 Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu 595 600 605 Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val 610 615 620 Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His Asn 625 630 635 640 Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser 645 650 655 Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn His 660 665 670 Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp 675 680 685 Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys 690 695 700 Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys Arg 705 710 715 720 Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg His 725 730 735 Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser Lys 740 745 750 Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr 755 760 765 Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile Leu 770 775 780 Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln 785 790 795 800 Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe 805 810 815 Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu Val 820 825 830 Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His Asn 835 840 845 Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg Ile 850 855 860 Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu 865 870 875 880 Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu Tyr 885 890 895 Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu 900 905 910 Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe 915 920 925 Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg Lys 930 935 940 Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg Lys 945 950 955 960 Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His Ala 965 970 975 Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val Thr Arg 980 985 990 Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys Lys 995 1000 1005 Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu Leu 1010 1015 1020 Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu 1025 1030 1035 Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser Arg 1040 1045 1050 Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr Ile 1055 1060 1065 Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile 1070 1075 1080 Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp 1085 1090 1095 Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu Ala 1100 1105 1110 Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys Ala 1115 1120 1125 Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly Asn 1130 1135 1140 Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe Val 1145 1150 1155 Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val Arg 1160 1165 1170 Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile 1175 1180 1185 Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val Val 1190 1195 1200 Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser 1205 1210 1215 Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu 1220 1225 1230 Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp 1235 1240 1245 Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro Ser 1250 1255 1260 Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp Leu 1265 1270 1275 Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val Arg 1280 1285 1290 Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg Pro 1295 1300 1305 Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 498 <211> 1321 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50150-nAPG07433.1 protein sequence" <400> 498 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp Ala Glu Leu Thr His Glu Tyr Trp Met Arg His Ala Leu Thr 35 40 45 Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Gln Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Arg Leu Ile Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Val Glu Val Val Glu Gly Ile Leu Arg Asp Glu Cys Ala Gly Met Leu 165 170 175 Cys Ala Phe Tyr Arg Gln Pro Arg Ala Val Lys Asn Ala Leu Lys Lys 180 185 190 Gly Ala Thr Asp Val Leu Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly 195 200 205 Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser Gly 210 215 220 Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu 225 230 235 240 Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser Trp 245 250 255 Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln Gly 260 265 270 Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser Leu 275 280 285 Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg 290 295 300 Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His Gly 305 310 315 320 Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys 325 330 335 Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu 340 345 350 Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg Arg 355 360 365 Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly 370 375 380 Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr 385 390 395 400 Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr 405 410 415 Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser Arg 420 425 430 Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg Arg 435 440 445 Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln 450 455 460 Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn 465 470 475 480 Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro 485 490 495 Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn 500 505 510 Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg 515 520 525 Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys 530 535 540 Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu 545 550 555 560 Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu 565 570 575 Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe 580 585 590 Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu 595 600 605 Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val 610 615 620 Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His Asn 625 630 635 640 Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser 645 650 655 Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn His 660 665 670 Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp 675 680 685 Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys 690 695 700 Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys Arg 705 710 715 720 Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg His 725 730 735 Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser Lys 740 745 750 Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr 755 760 765 Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile Leu 770 775 780 Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln 785 790 795 800 Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe 805 810 815 Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu Val 820 825 830 Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His Asn 835 840 845 Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg Ile 850 855 860 Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu 865 870 875 880 Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu Tyr 885 890 895 Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu 900 905 910 Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe 915 920 925 Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg Lys 930 935 940 Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg Lys 945 950 955 960 Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His Ala 965 970 975 Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val Thr Arg 980 985 990 Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys Lys 995 1000 1005 Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu Leu 1010 1015 1020 Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu 1025 1030 1035 Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser Arg 1040 1045 1050 Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr Ile 1055 1060 1065 Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile 1070 1075 1080 Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp 1085 1090 1095 Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu Ala 1100 1105 1110 Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys Ala 1115 1120 1125 Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly Asn 1130 1135 1140 Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe Val 1145 1150 1155 Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val Arg 1160 1165 1170 Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile 1175 1180 1185 Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val Val 1190 1195 1200 Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser 1205 1210 1215 Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu 1220 1225 1230 Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp 1235 1240 1245 Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro Ser 1250 1255 1260 Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp Leu 1265 1270 1275 Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val Arg 1280 1285 1290 Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg Pro 1295 1300 1305 Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 499 <211> 1323 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50151-nAPG07433.1 protein sequence" <400> 499 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp Leu Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu Gln 35 40 45 Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Tyr Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Thr Leu Val Phe Gly Val Arg Asn Glu Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Met Asn Val Leu Arg Tyr Pro Gly Met Asn His Gln 145 150 155 160 Val Gln Ile Ile Asp Gly Val Leu Ala Pro Glu Cys Ser Gly Leu Leu 165 170 175 Cys Asp Phe Tyr Arg Met Pro Arg Gln Gln Lys Asn Gln Gln Lys Ala 180 185 190 Glu Ser Thr Ser Ser Pro Gly Asp Ser Gly Gly Ser Ser Gly Gly Ser 195 200 205 Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser 210 215 220 Ser Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile 225 230 235 240 Gly Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu 245 250 255 Ser Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp 260 265 270 Gln Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala 275 280 285 Ser Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu 290 295 300 Asn Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln 305 310 315 320 His Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser 325 330 335 Lys Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg 340 345 350 Leu Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln 355 360 365 Arg Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu 370 375 380 Thr Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser 385 390 395 400 Leu Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser 405 410 415 Lys Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val 420 425 430 Ser Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln 435 440 445 Arg Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr 450 455 460 Leu Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile 465 470 475 480 Leu Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg 485 490 495 Ile Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln 500 505 510 Val Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu 515 520 525 Gln Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr 530 535 540 Lys Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp 545 550 555 560 Leu Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro 565 570 575 Asn Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys 580 585 590 Ala Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr 595 600 605 Asn Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu 610 615 620 Thr Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser 625 630 635 640 His Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu 645 650 655 Leu Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile 660 665 670 Asn His Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala 675 680 685 Val Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg 690 695 700 Ser Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val 705 710 715 720 Lys Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg 725 730 735 Arg His Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu 740 745 750 Ser Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu 755 760 765 Asn Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly 770 775 780 Ile Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys 785 790 795 800 Glu Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp 805 810 815 Thr Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu 820 825 830 Glu Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr 835 840 845 His Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn 850 855 860 Arg Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala 865 870 875 880 Phe Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg 885 890 895 Glu Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile 900 905 910 Lys Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys 915 920 925 Asn Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro 930 935 940 Arg Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe 945 950 955 960 Arg Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His 965 970 975 His Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val 980 985 990 Thr Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val 995 1000 1005 Lys Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu 1010 1015 1020 Leu Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser 1025 1030 1035 Glu Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val 1040 1045 1050 Ser Arg Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln 1055 1060 1065 Thr Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile 1070 1075 1080 Ile Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn 1085 1090 1095 Gly Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr 1100 1105 1110 Glu Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys 1115 1120 1125 Lys Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr 1130 1135 1140 Gly Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser 1145 1150 1155 Phe Val Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu 1160 1165 1170 Val Arg Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val 1175 1180 1185 Pro Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys 1190 1195 1200 Val Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp 1205 1210 1215 Asn Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val 1220 1225 1230 Arg Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr 1235 1240 1245 Leu Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys 1250 1255 1260 Pro Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu 1265 1270 1275 Asp Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu 1280 1285 1290 Val Arg Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys 1295 1300 1305 Arg Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 500 <211> 1321 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50152-nAPG07433.1 protein sequence" <400> 500 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp Asn Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu Gly 35 40 45 Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Thr Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Thr Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Val Glu Ile Val Glu Gly Ile Leu Ser Glu Ser Cys Ala Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg Gln Pro Arg Ala Val Lys Asn Ala Leu Lys Lys 180 185 190 Ala Ala Asp Pro Ala Ala Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly 195 200 205 Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser Gly 210 215 220 Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu 225 230 235 240 Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser Trp 245 250 255 Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln Gly 260 265 270 Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser Leu 275 280 285 Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg 290 295 300 Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His Gly 305 310 315 320 Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys 325 330 335 Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu 340 345 350 Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg Arg 355 360 365 Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly 370 375 380 Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr 385 390 395 400 Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr 405 410 415 Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser Arg 420 425 430 Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg Arg 435 440 445 Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln 450 455 460 Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn 465 470 475 480 Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro 485 490 495 Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn 500 505 510 Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg 515 520 525 Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys 530 535 540 Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu 545 550 555 560 Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu 565 570 575 Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe 580 585 590 Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu 595 600 605 Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val 610 615 620 Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His Asn 625 630 635 640 Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser 645 650 655 Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn His 660 665 670 Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp 675 680 685 Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys 690 695 700 Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys Arg 705 710 715 720 Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg His 725 730 735 Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser Lys 740 745 750 Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr 755 760 765 Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile Leu 770 775 780 Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln 785 790 795 800 Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe 805 810 815 Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu Val 820 825 830 Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His Asn 835 840 845 Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg Ile 850 855 860 Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu 865 870 875 880 Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu Tyr 885 890 895 Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu 900 905 910 Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe 915 920 925 Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg Lys 930 935 940 Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg Lys 945 950 955 960 Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His Ala 965 970 975 Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val Thr Arg 980 985 990 Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys Lys 995 1000 1005 Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu Leu 1010 1015 1020 Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu 1025 1030 1035 Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser Arg 1040 1045 1050 Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr Ile 1055 1060 1065 Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile 1070 1075 1080 Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp 1085 1090 1095 Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu Ala 1100 1105 1110 Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys Ala 1115 1120 1125 Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly Asn 1130 1135 1140 Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe Val 1145 1150 1155 Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val Arg 1160 1165 1170 Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile 1175 1180 1185 Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val Val 1190 1195 1200 Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser 1205 1210 1215 Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu 1220 1225 1230 Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp 1235 1240 1245 Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro Ser 1250 1255 1260 Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp Leu 1265 1270 1275 Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val Arg 1280 1285 1290 Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg Pro 1295 1300 1305 Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 501 <211> 1318 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50153-nAPG07433.1 protein sequence" <400> 501 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp Thr Glu Phe Thr His Glu His Trp Met Arg His Ala Leu Thr 35 40 45 Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly His Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ile Gly Ser Leu Met Asn Val Leu Gly Tyr Pro Gly Met Asn His Gln 145 150 155 160 Val Gln Val Ser Glu Gly Val Leu Ala Thr Glu Cys Ser Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg Ala Pro Arg Leu Val Lys Asn Ala Leu Lys Glu 180 185 190 Lys Ala Arg Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Ser Glu Thr 195 200 205 Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser Gly Gly Ser Ser 210 215 220 Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu Ala Ile Gly 225 230 235 240 Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser Trp Asn Lys Asp 245 250 255 Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln Gly Val Arg Met 260 265 270 Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser Leu Ala Glu Pro 275 280 285 Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys Ser Gln 290 295 300 Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His Gly Val Ile Thr 305 310 315 320 Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys Ser Met Asp 325 330 335 Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn His Phe 340 345 350 Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly Phe Lys 355 360 365 Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly Lys Val Leu 370 375 380 Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr Arg Thr Val 385 390 395 400 Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr Asp Arg Lys 405 410 415 Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala Glu Leu 420 425 430 Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg Arg Phe Gln Ser 435 440 445 Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln Ile Trp Thr 450 455 460 His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys Val Gly 465 470 475 480 Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys Ala Thr 485 490 495 Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg Thr Arg 500 505 510 Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg Glu Ile Ile 515 520 525 Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys Thr Ile 530 535 540 Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu Asp Glu 545 550 555 560 Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu Leu Lys 565 570 575 Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr Glu Ile 580 585 590 Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu Thr Phe Ser 595 600 605 Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val Tyr Lys Thr 610 615 620 Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His Asn Leu Pro Lys 625 630 635 640 Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser Leu Ser Tyr 645 650 655 Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn His Val Leu Ser 660 665 670 Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp Gln Leu Gly 675 680 685 Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys Phe Leu Pro 690 695 700 Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala Leu Thr 705 710 715 720 Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg His Gly Ser Pro 725 730 735 His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser Lys Asn His Asp 740 745 750 Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr Lys Lys Asn 755 760 765 Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile Leu Asn Pro Thr 770 775 780 Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly Glu Arg 785 790 795 800 Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe Phe Asn Glu 805 810 815 Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu Val Asp His Ile 820 825 830 Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His Asn Lys Val Leu 835 840 845 Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg Ile Pro Tyr Thr 850 855 860 Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu Arg Tyr Val 865 870 875 880 Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu Tyr Leu Leu Lys 885 890 895 Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu Arg His Leu 900 905 910 Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe Ile Glu Gln 915 920 925 Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg Lys Arg Arg Val 930 935 940 Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg Lys Arg Trp Gly 945 950 955 960 Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His Ala Met Asp Ala 965 970 975 Ile Ile Val Ala Cys Thr Asp His His Met Val Thr Arg Val Thr Glu 980 985 990 Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys Lys Pro Tyr Phe 995 1000 1005 Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu Leu Ser His Leu 1010 1015 1020 Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu Leu Lys Ala 1025 1030 1035 Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser Arg Met Pro Lys 1040 1045 1050 Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr Ile Met Arg Lys 1055 1060 1065 Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile Glu Arg Leu 1070 1075 1080 His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp Phe Lys Met 1085 1090 1095 Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu Ala Ile Lys Gln 1100 1105 1110 Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys Ala Phe Glu Thr 1115 1120 1125 Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly Asn Leu Ile Lys 1130 1135 1140 Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe Val Arg Glu Val 1145 1150 1155 Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val Arg Val Asp Leu 1160 1165 1170 Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile Tyr Val Pro 1175 1180 1185 Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val Val Ala Ser Ser 1190 1195 1200 Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser Phe Thr Phe 1205 1210 1215 Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu Val Lys Gly 1220 1225 1230 Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp Ile Asp Ser 1235 1240 1245 Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro Ser Lys Lys Asn 1250 1255 1260 Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp Leu Glu Lys Tyr 1265 1270 1275 Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val Arg Lys Glu Thr 1280 1285 1290 Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg Pro Ala Ala Thr 1295 1300 1305 Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 <210> 502 <211> 1325 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50154-nAPG07433.1 protein sequence" <400> 502 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Glu Ser Glu Phe Thr His Glu His Trp Met Arg His Ala Leu Thr 35 40 45 Leu Ala Arg Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Ser Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Gly 115 120 125 Arg Ile Gly Asn Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ile Gly Ser Leu Met Asn Val Val Gly Tyr Pro Gly Met Asn His Gln 145 150 155 160 Ile Asn Val Ile Glu Gly Val Leu Ala Glu Glu Cys Ser Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg Ala Pro Arg Leu Val Lys Asn Ala Leu Lys Glu 180 185 190 Lys Ala Arg Asn Gly Asn Asn Pro Asn Lys Ser Gly Gly Ser Ser Gly 195 200 205 Gly Ser Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro 210 215 220 Glu Ser Ser Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr 225 230 235 240 Arg Ile Gly Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile 245 250 255 Glu Leu Ser Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile 260 265 270 Val Asp Gln Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr 275 280 285 Gly Ala Ser Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg 290 295 300 Arg Leu Asn Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu 305 310 315 320 Val Gln His Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro 325 330 335 Leu Ser Lys Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu 340 345 350 Asp Arg Leu Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu 355 360 365 Ala Gln Arg Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp 370 375 380 Thr Glu Thr Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg 385 390 395 400 Leu Ser Leu Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp 405 410 415 Phe Ser Lys Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe 420 425 430 Ser Val Ser Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala 435 440 445 Ala Gln Arg Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu 450 455 460 Thr Tyr Leu Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn 465 470 475 480 Ala Ile Leu Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu 485 490 495 Arg Arg Ile Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu 500 505 510 Asp Gln Val Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr 515 520 525 Lys Glu Gln Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp 530 535 540 Tyr Tyr Lys Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg 545 550 555 560 Lys Trp Leu Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr 565 570 575 Asp Pro Asn Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn 580 585 590 Leu Lys Ala Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu 595 600 605 Arg Thr Asn Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr 610 615 620 Ala Leu Thr Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys 625 630 635 640 Ser Ser His Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu 645 650 655 Glu Leu Leu Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys 660 665 670 Ala Ile Asn His Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys 675 680 685 Glu Ala Val Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu 690 695 700 Lys Arg Ser Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro 705 710 715 720 Ile Val Lys Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile 725 730 735 Ile Arg Arg His Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg 740 745 750 Glu Leu Ser Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln 755 760 765 Asp Glu Asn Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu 770 775 780 His Gly Ile Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu 785 790 795 800 Trp Lys Glu Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro 805 810 815 Ala Asp Thr Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro 820 825 830 Ile Leu Glu Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp 835 840 845 Ser Tyr His Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys 850 855 860 Gly Asn Arg Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp 865 870 875 880 Glu Ala Phe Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys 885 890 895 Lys Arg Glu Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu 900 905 910 Leu Ile Lys Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe 915 920 925 Leu Lys Asn Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp 930 935 940 Asn Pro Arg Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala 945 950 955 960 His Phe Arg Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr 965 970 975 Leu His His Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His 980 985 990 Met Val Thr Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys 995 1000 1005 Ser Val Lys Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg 1010 1015 1020 Asp Glu Leu Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys 1025 1030 1035 Ile Ser Glu Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile 1040 1045 1050 Phe Val Ser Arg Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His 1055 1060 1065 Lys Gln Thr Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys 1070 1075 1080 Thr Ile Ile Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp 1085 1090 1095 Glu Asn Gly Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala 1100 1105 1110 Thr Tyr Glu Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn 1115 1120 1125 Ser Lys Lys Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys 1130 1135 1140 Gly Thr Gly Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala 1145 1150 1155 Lys Ser Phe Val Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly 1160 1165 1170 Asp Leu Val Arg Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr 1175 1180 1185 Met Val Pro Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro 1190 1195 1200 Lys Lys Val Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr 1205 1210 1215 Leu Asp Asn Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp 1220 1225 1230 Leu Val Arg Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe 1235 1240 1245 Gly Thr Leu Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val 1250 1255 1260 Asn Lys Pro Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr 1265 1270 1275 Ile Glu Asp Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu 1280 1285 1290 Arg Leu Val Arg Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly 1295 1300 1305 Ser Lys Arg Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys 1310 1315 1320 Lys Lys 1325 <210> 503 <211> 1318 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50155-nAPG07433.1 protein sequence" <400> 503 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asn Pro Glu Leu Thr His Glu His Trp Met Arg Tyr Ala Leu Thr 35 40 45 Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Gln Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Ile Glu Phe Thr Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg Gln Pro Arg Leu Val Lys Asn Ala Leu Lys Thr 180 185 190 Gly Asn Ala Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Ser Glu Thr 195 200 205 Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser Gly Gly Ser Ser 210 215 220 Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu Ala Ile Gly 225 230 235 240 Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser Trp Asn Lys Asp 245 250 255 Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln Gly Val Arg Met 260 265 270 Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser Leu Ala Glu Pro 275 280 285 Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys Ser Gln 290 295 300 Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His Gly Val Ile Thr 305 310 315 320 Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys Ser Met Asp 325 330 335 Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn His Phe 340 345 350 Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly Phe Lys 355 360 365 Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly Lys Val Leu 370 375 380 Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr Arg Thr Val 385 390 395 400 Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr Asp Arg Lys 405 410 415 Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala Glu Leu 420 425 430 Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg Arg Phe Gln Ser 435 440 445 Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln Ile Trp Thr 450 455 460 His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys Val Gly 465 470 475 480 Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys Ala Thr 485 490 495 Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg Thr Arg 500 505 510 Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg Glu Ile Ile 515 520 525 Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys Thr Ile 530 535 540 Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu Asp Glu 545 550 555 560 Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu Leu Lys 565 570 575 Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr Glu Ile 580 585 590 Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu Thr Phe Ser 595 600 605 Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val Tyr Lys Thr 610 615 620 Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His Asn Leu Pro Lys 625 630 635 640 Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser Leu Ser Tyr 645 650 655 Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn His Val Leu Ser 660 665 670 Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp Gln Leu Gly 675 680 685 Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys Phe Leu Pro 690 695 700 Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala Leu Thr 705 710 715 720 Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg His Gly Ser Pro 725 730 735 His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser Lys Asn His Asp 740 745 750 Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr Lys Lys Asn 755 760 765 Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile Leu Asn Pro Thr 770 775 780 Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly Glu Arg 785 790 795 800 Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe Phe Asn Glu 805 810 815 Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu Val Asp His Ile 820 825 830 Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His Asn Lys Val Leu 835 840 845 Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg Ile Pro Tyr Thr 850 855 860 Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu Arg Tyr Val 865 870 875 880 Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu Tyr Leu Leu Lys 885 890 895 Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu Arg His Leu 900 905 910 Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe Ile Glu Gln 915 920 925 Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg Lys Arg Arg Val 930 935 940 Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg Lys Arg Trp Gly 945 950 955 960 Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His Ala Met Asp Ala 965 970 975 Ile Ile Val Ala Cys Thr Asp His His Met Val Thr Arg Val Thr Glu 980 985 990 Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys Lys Pro Tyr Phe 995 1000 1005 Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu Leu Ser His Leu 1010 1015 1020 Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu Leu Lys Ala 1025 1030 1035 Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser Arg Met Pro Lys 1040 1045 1050 Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr Ile Met Arg Lys 1055 1060 1065 Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile Glu Arg Leu 1070 1075 1080 His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp Phe Lys Met 1085 1090 1095 Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu Ala Ile Lys Gln 1100 1105 1110 Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys Ala Phe Glu Thr 1115 1120 1125 Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly Asn Leu Ile Lys 1130 1135 1140 Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe Val Arg Glu Val 1145 1150 1155 Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val Arg Val Asp Leu 1160 1165 1170 Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile Tyr Val Pro 1175 1180 1185 Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val Val Ala Ser Ser 1190 1195 1200 Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser Phe Thr Phe 1205 1210 1215 Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu Val Lys Gly 1220 1225 1230 Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp Ile Asp Ser 1235 1240 1245 Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro Ser Lys Lys Asn 1250 1255 1260 Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp Leu Glu Lys Tyr 1265 1270 1275 Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val Arg Lys Glu Thr 1280 1285 1290 Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg Pro Ala Ala Thr 1295 1300 1305 Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 <210> 504 <211> 1320 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50156-nAPG07433.1 protein sequence" <400> 504 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp Pro Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu Gln 35 40 45 Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Ile His Ser 115 120 125 Arg Ile Gly Thr Val Val Phe Gly Val Arg Asn Glu Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Leu Asn Val Leu Arg Tyr Pro Gly Met Asn His Gln 145 150 155 160 Val Asn Val Leu Gly Gly Val Leu Ala Pro Ala Cys Ser Glu Met Leu 165 170 175 Cys Glu Phe Tyr Arg Met Pro Arg Gln Gln Lys Asn Arg Gln Lys Ala 180 185 190 Glu Ser Lys Leu Ser Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Ser 195 200 205 Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser Gly Gly 210 215 220 Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu Ala 225 230 235 240 Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser Trp Asn 245 250 255 Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln Gly Val 260 265 270 Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser Leu Ala 275 280 285 Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys 290 295 300 Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His Gly Val 305 310 315 320 Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys Ser 325 330 335 Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn 340 345 350 His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly 355 360 365 Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly Lys 370 375 380 Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr Arg 385 390 395 400 Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr Asp 405 410 415 Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala 420 425 430 Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg Arg Phe 435 440 445 Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln Ile 450 455 460 Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys 465 470 475 480 Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys 485 490 495 Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg 500 505 510 Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg Glu 515 520 525 Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys 530 535 540 Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu 545 550 555 560 Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu 565 570 575 Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr 580 585 590 Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu Thr 595 600 605 Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val Tyr 610 615 620 Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His Asn Leu 625 630 635 640 Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser Leu 645 650 655 Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn His Val 660 665 670 Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp Gln 675 680 685 Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys Phe 690 695 700 Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala 705 710 715 720 Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg His Gly 725 730 735 Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser Lys Asn 740 745 750 His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr Lys 755 760 765 Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile Leu Asn 770 775 780 Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly 785 790 795 800 Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe Phe 805 810 815 Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu Val Asp 820 825 830 His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His Asn Lys 835 840 845 Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg Ile Pro 850 855 860 Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu Arg 865 870 875 880 Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu Tyr Leu 885 890 895 Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu Arg 900 905 910 His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe Ile 915 920 925 Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg Lys Arg 930 935 940 Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg Lys Arg 945 950 955 960 Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His Ala Met 965 970 975 Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val Thr Arg Val 980 985 990 Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys Lys Pro 995 1000 1005 Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu Leu Ser 1010 1015 1020 His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu Leu 1025 1030 1035 Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser Arg Met 1040 1045 1050 Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr Ile Met 1055 1060 1065 Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile Glu 1070 1075 1080 Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp Phe 1085 1090 1095 Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu Ala Ile 1100 1105 1110 Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys Ala Phe 1115 1120 1125 Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly Asn Leu 1130 1135 1140 Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe Val Arg 1145 1150 1155 Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val Arg Val 1160 1165 1170 Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile Tyr 1175 1180 1185 Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val Val Ala 1190 1195 1200 Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser Phe 1205 1210 1215 Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu Val 1220 1225 1230 Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp Ile 1235 1240 1245 Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro Ser Lys 1250 1255 1260 Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp Leu Glu 1265 1270 1275 Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val Arg Lys 1280 1285 1290 Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg Pro Ala 1295 1300 1305 Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 505 <211> 1320 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50157-nAPG07433.1 protein sequence" <400> 505 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp Asn Glu Leu Asn His Glu His Trp Met Arg His Ala Leu Thr 35 40 45 Leu Ala Gln Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Gln Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Met Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Gln Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Val Glu Ile Thr Glu Gly Val Leu Ala Asp Asp Cys Ser Ser Met Leu 165 170 175 Cys Asp Phe Tyr Arg His Pro Arg Glu Gln Lys Asn Ala Leu Lys Arg 180 185 190 Ala Ala His Ser Asn Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Ser 195 200 205 Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser Gly Gly 210 215 220 Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu Ala 225 230 235 240 Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser Trp Asn 245 250 255 Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln Gly Val 260 265 270 Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser Leu Ala 275 280 285 Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys 290 295 300 Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His Gly Val 305 310 315 320 Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys Ser 325 330 335 Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn 340 345 350 His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly 355 360 365 Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly Lys 370 375 380 Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr Arg 385 390 395 400 Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr Asp 405 410 415 Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala 420 425 430 Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg Arg Phe 435 440 445 Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln Ile 450 455 460 Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys 465 470 475 480 Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys 485 490 495 Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg 500 505 510 Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg Glu 515 520 525 Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys 530 535 540 Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu 545 550 555 560 Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu 565 570 575 Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr 580 585 590 Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu Thr 595 600 605 Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val Tyr 610 615 620 Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His Asn Leu 625 630 635 640 Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser Leu 645 650 655 Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn His Val 660 665 670 Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp Gln 675 680 685 Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys Phe 690 695 700 Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala 705 710 715 720 Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg His Gly 725 730 735 Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser Lys Asn 740 745 750 His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr Lys 755 760 765 Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile Leu Asn 770 775 780 Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly 785 790 795 800 Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe Phe 805 810 815 Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu Val Asp 820 825 830 His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His Asn Lys 835 840 845 Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg Ile Pro 850 855 860 Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu Arg 865 870 875 880 Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu Tyr Leu 885 890 895 Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu Arg 900 905 910 His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe Ile 915 920 925 Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg Lys Arg 930 935 940 Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg Lys Arg 945 950 955 960 Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His Ala Met 965 970 975 Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val Thr Arg Val 980 985 990 Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys Lys Pro 995 1000 1005 Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu Leu Ser 1010 1015 1020 His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu Leu 1025 1030 1035 Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser Arg Met 1040 1045 1050 Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr Ile Met 1055 1060 1065 Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile Glu 1070 1075 1080 Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp Phe 1085 1090 1095 Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu Ala Ile 1100 1105 1110 Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys Ala Phe 1115 1120 1125 Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly Asn Leu 1130 1135 1140 Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe Val Arg 1145 1150 1155 Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val Arg Val 1160 1165 1170 Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile Tyr 1175 1180 1185 Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val Val Ala 1190 1195 1200 Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser Phe 1205 1210 1215 Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu Val 1220 1225 1230 Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp Ile 1235 1240 1245 Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro Ser Lys 1250 1255 1260 Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp Leu Glu 1265 1270 1275 Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val Arg Lys 1280 1285 1290 Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg Pro Ala 1295 1300 1305 Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 506 <211> 1322 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50158-nAPG07433.1 protein sequence" <400> 506 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asn Pro Glu His Asn His Glu Tyr Trp Met Arg His Ala Leu Thr 35 40 45 Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Tyr Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Thr Leu Val Phe Gly Val Arg Asn Glu Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Met Asn Val Leu Gly Tyr Pro Gly Met Asn His Gln 145 150 155 160 Val Gln Thr Ile Gly Gly Val Leu Ala Pro Glu Cys Ser Gly Leu Leu 165 170 175 Cys Asp Phe Tyr Arg Met Pro Arg Gln Gln Lys Asn Gln Gln Lys Ala 180 185 190 Glu Leu Asn Gln Pro Gly Asp Ser Gly Gly Ser Ser Gly Gly Ser Ser 195 200 205 Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser 210 215 220 Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly 225 230 235 240 Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser 245 250 255 Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln 260 265 270 Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser 275 280 285 Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn 290 295 300 Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His 305 310 315 320 Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys 325 330 335 Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu 340 345 350 Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg 355 360 365 Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr 370 375 380 Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu 385 390 395 400 Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys 405 410 415 Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser 420 425 430 Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg 435 440 445 Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu 450 455 460 Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu 465 470 475 480 Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile 485 490 495 Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val 500 505 510 Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln 515 520 525 Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys 530 535 540 Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu 545 550 555 560 Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn 565 570 575 Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala 580 585 590 Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn 595 600 605 Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr 610 615 620 Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His 625 630 635 640 Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu 645 650 655 Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn 660 665 670 His Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val 675 680 685 Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser 690 695 700 Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys 705 710 715 720 Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg 725 730 735 His Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser 740 745 750 Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn 755 760 765 Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile 770 775 780 Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu 785 790 795 800 Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr 805 810 815 Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu 820 825 830 Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His 835 840 845 Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg 850 855 860 Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe 865 870 875 880 Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu 885 890 895 Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys 900 905 910 Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn 915 920 925 Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg 930 935 940 Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg 945 950 955 960 Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His 965 970 975 Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val Thr 980 985 990 Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys 995 1000 1005 Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu 1010 1015 1020 Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu 1025 1030 1035 Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser 1040 1045 1050 Arg Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr 1055 1060 1065 Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile 1070 1075 1080 Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly 1085 1090 1095 Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu 1100 1105 1110 Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys 1115 1120 1125 Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly 1130 1135 1140 Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe 1145 1150 1155 Val Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val 1160 1165 1170 Arg Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro 1175 1180 1185 Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val 1190 1195 1200 Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn 1205 1210 1215 Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg 1220 1225 1230 Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu 1235 1240 1245 Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro 1250 1255 1260 Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp 1265 1270 1275 Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val 1280 1285 1290 Arg Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg 1295 1300 1305 Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 507 <211> 1322 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50159-nAPG07433.1 protein sequence" <400> 507 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp Leu Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu Ser 35 40 45 Leu Ala Lys Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Thr Leu Val Tyr Gly Val Arg Asn Glu Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Met Asn Val Leu Gly Tyr Pro Gly Met Asn His Gln 145 150 155 160 Val Gln Ile Ile Gly Gly Val Leu Ala Pro Asp Cys Ser Gly Leu Leu 165 170 175 Cys Asp Phe Tyr Arg Met Pro Arg Gln Gln Lys Asn Gln Gln Lys Ala 180 185 190 Glu Leu Lys Ser Ser Gly Asp Ser Gly Gly Ser Ser Gly Gly Ser Ser 195 200 205 Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser 210 215 220 Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly 225 230 235 240 Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser 245 250 255 Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln 260 265 270 Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser 275 280 285 Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn 290 295 300 Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His 305 310 315 320 Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys 325 330 335 Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu 340 345 350 Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg 355 360 365 Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr 370 375 380 Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu 385 390 395 400 Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys 405 410 415 Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser 420 425 430 Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg 435 440 445 Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu 450 455 460 Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu 465 470 475 480 Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile 485 490 495 Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val 500 505 510 Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln 515 520 525 Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys 530 535 540 Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu 545 550 555 560 Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn 565 570 575 Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala 580 585 590 Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn 595 600 605 Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr 610 615 620 Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His 625 630 635 640 Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu 645 650 655 Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn 660 665 670 His Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val 675 680 685 Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser 690 695 700 Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys 705 710 715 720 Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg 725 730 735 His Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser 740 745 750 Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn 755 760 765 Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile 770 775 780 Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu 785 790 795 800 Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr 805 810 815 Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu 820 825 830 Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His 835 840 845 Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg 850 855 860 Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe 865 870 875 880 Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu 885 890 895 Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys 900 905 910 Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn 915 920 925 Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg 930 935 940 Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg 945 950 955 960 Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His 965 970 975 Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val Thr 980 985 990 Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys 995 1000 1005 Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu 1010 1015 1020 Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu 1025 1030 1035 Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser 1040 1045 1050 Arg Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr 1055 1060 1065 Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile 1070 1075 1080 Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly 1085 1090 1095 Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu 1100 1105 1110 Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys 1115 1120 1125 Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly 1130 1135 1140 Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe 1145 1150 1155 Val Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val 1160 1165 1170 Arg Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro 1175 1180 1185 Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val 1190 1195 1200 Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn 1205 1210 1215 Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg 1220 1225 1230 Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu 1235 1240 1245 Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro 1250 1255 1260 Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp 1265 1270 1275 Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val 1280 1285 1290 Arg Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg 1295 1300 1305 Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 508 <211> 1320 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50160-nAPG07433.1 protein sequence" <400> 508 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp His Glu Phe Asn Asp Glu Tyr Trp Met Arg His Ala Leu Thr 35 40 45 Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Ala Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Ser Arg Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Val Glu Ile Thr Glu Gly Ile Leu Ala Glu Ser Cys Ser Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg Trp Pro Arg Glu Val Lys Asn Ala Leu Lys Lys 180 185 190 Ala Arg Gln Glu Glu Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Ser 195 200 205 Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser Gly Gly 210 215 220 Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu Ala 225 230 235 240 Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser Trp Asn 245 250 255 Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln Gly Val 260 265 270 Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser Leu Ala 275 280 285 Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys 290 295 300 Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His Gly Val 305 310 315 320 Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys Ser 325 330 335 Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn 340 345 350 His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly 355 360 365 Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly Lys 370 375 380 Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr Arg 385 390 395 400 Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr Asp 405 410 415 Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala 420 425 430 Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg Arg Phe 435 440 445 Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln Ile 450 455 460 Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys 465 470 475 480 Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys 485 490 495 Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg 500 505 510 Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg Glu 515 520 525 Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys 530 535 540 Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu 545 550 555 560 Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu 565 570 575 Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr 580 585 590 Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu Thr 595 600 605 Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val Tyr 610 615 620 Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His Asn Leu 625 630 635 640 Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser Leu 645 650 655 Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn His Val 660 665 670 Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp Gln 675 680 685 Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys Phe 690 695 700 Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala 705 710 715 720 Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg His Gly 725 730 735 Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser Lys Asn 740 745 750 His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr Lys 755 760 765 Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile Leu Asn 770 775 780 Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly 785 790 795 800 Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe Phe 805 810 815 Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu Val Asp 820 825 830 His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His Asn Lys 835 840 845 Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg Ile Pro 850 855 860 Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu Arg 865 870 875 880 Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu Tyr Leu 885 890 895 Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu Arg 900 905 910 His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe Ile 915 920 925 Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg Lys Arg 930 935 940 Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg Lys Arg 945 950 955 960 Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His Ala Met 965 970 975 Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val Thr Arg Val 980 985 990 Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys Lys Pro 995 1000 1005 Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu Leu Ser 1010 1015 1020 His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu Leu 1025 1030 1035 Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser Arg Met 1040 1045 1050 Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr Ile Met 1055 1060 1065 Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile Glu 1070 1075 1080 Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp Phe 1085 1090 1095 Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu Ala Ile 1100 1105 1110 Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys Ala Phe 1115 1120 1125 Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly Asn Leu 1130 1135 1140 Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe Val Arg 1145 1150 1155 Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val Arg Val 1160 1165 1170 Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile Tyr 1175 1180 1185 Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val Val Ala 1190 1195 1200 Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser Phe 1205 1210 1215 Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu Val 1220 1225 1230 Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp Ile 1235 1240 1245 Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro Ser Lys 1250 1255 1260 Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp Leu Glu 1265 1270 1275 Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val Arg Lys 1280 1285 1290 Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg Pro Ala 1295 1300 1305 Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 509 <211> 1320 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50161-nAPG07433.1 protein sequence" <400> 509 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Gln Thr Glu Leu Thr His Glu Tyr Trp Met Arg His Ala Leu Thr 35 40 45 Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Gly 115 120 125 Arg Ile Gly Thr Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Val Gly Ser Leu Met Asn Ile Thr Gly Tyr Pro Gly Met Asn His Gln 145 150 155 160 Val Gln Val Ile Glu Gly Ile Leu Ala Thr Glu Cys Ser Ala Met Leu 165 170 175 Cys Ala Phe Tyr Arg Gln Pro Arg Leu Val Lys Asn Ala Leu Lys Glu 180 185 190 Ala Ala Lys Thr Ala Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Ser 195 200 205 Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser Gly Gly 210 215 220 Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu Ala 225 230 235 240 Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser Trp Asn 245 250 255 Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln Gly Val 260 265 270 Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser Leu Ala 275 280 285 Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys 290 295 300 Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His Gly Val 305 310 315 320 Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys Ser 325 330 335 Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn 340 345 350 His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly 355 360 365 Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly Lys 370 375 380 Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr Arg 385 390 395 400 Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr Asp 405 410 415 Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala 420 425 430 Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg Arg Phe 435 440 445 Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln Ile 450 455 460 Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys 465 470 475 480 Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys 485 490 495 Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg 500 505 510 Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg Glu 515 520 525 Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys 530 535 540 Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu 545 550 555 560 Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu 565 570 575 Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr 580 585 590 Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu Thr 595 600 605 Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val Tyr 610 615 620 Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His Asn Leu 625 630 635 640 Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser Leu 645 650 655 Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn His Val 660 665 670 Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp Gln 675 680 685 Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys Phe 690 695 700 Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala 705 710 715 720 Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg His Gly 725 730 735 Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser Lys Asn 740 745 750 His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr Lys 755 760 765 Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile Leu Asn 770 775 780 Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly 785 790 795 800 Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe Phe 805 810 815 Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu Val Asp 820 825 830 His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His Asn Lys 835 840 845 Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg Ile Pro 850 855 860 Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu Arg 865 870 875 880 Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu Tyr Leu 885 890 895 Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu Arg 900 905 910 His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe Ile 915 920 925 Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg Lys Arg 930 935 940 Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg Lys Arg 945 950 955 960 Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His Ala Met 965 970 975 Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val Thr Arg Val 980 985 990 Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys Lys Pro 995 1000 1005 Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu Leu Ser 1010 1015 1020 His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu Leu 1025 1030 1035 Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser Arg Met 1040 1045 1050 Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr Ile Met 1055 1060 1065 Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile Glu 1070 1075 1080 Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp Phe 1085 1090 1095 Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu Ala Ile 1100 1105 1110 Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys Ala Phe 1115 1120 1125 Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly Asn Leu 1130 1135 1140 Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe Val Arg 1145 1150 1155 Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val Arg Val 1160 1165 1170 Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile Tyr 1175 1180 1185 Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val Val Ala 1190 1195 1200 Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser Phe 1205 1210 1215 Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu Val 1220 1225 1230 Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp Ile 1235 1240 1245 Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro Ser Lys 1250 1255 1260 Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp Leu Glu 1265 1270 1275 Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val Arg Lys 1280 1285 1290 Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg Pro Ala 1295 1300 1305 Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 510 <211> 1321 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50162-nAPG07433.1 protein sequence" <400> 510 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asn Pro Glu Leu Asn His Asp Tyr Trp Met Arg His Ala Leu Ser 35 40 45 Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Arg Asn Asn Glu Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Met Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Gln Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Val Glu Ile Val Glu Gly Val Leu Arg Asp Glu Cys Ala Gly Met Leu 165 170 175 Cys Asp Phe Tyr Arg Gln Pro Arg Leu Val Lys Asn Ala Gln Lys Lys 180 185 190 Gly Ala Glu Pro Leu Ile Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly 195 200 205 Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser Gly 210 215 220 Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu 225 230 235 240 Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser Trp 245 250 255 Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln Gly 260 265 270 Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser Leu 275 280 285 Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg 290 295 300 Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His Gly 305 310 315 320 Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys 325 330 335 Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu 340 345 350 Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg Arg 355 360 365 Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly 370 375 380 Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr 385 390 395 400 Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr 405 410 415 Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser Arg 420 425 430 Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg Arg 435 440 445 Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln 450 455 460 Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn 465 470 475 480 Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro 485 490 495 Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn 500 505 510 Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg 515 520 525 Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys 530 535 540 Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu 545 550 555 560 Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu 565 570 575 Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe 580 585 590 Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu 595 600 605 Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val 610 615 620 Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His Asn 625 630 635 640 Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser 645 650 655 Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn His 660 665 670 Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp 675 680 685 Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys 690 695 700 Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys Arg 705 710 715 720 Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg His 725 730 735 Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser Lys 740 745 750 Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr 755 760 765 Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile Leu 770 775 780 Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln 785 790 795 800 Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe 805 810 815 Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu Val 820 825 830 Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His Asn 835 840 845 Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg Ile 850 855 860 Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu 865 870 875 880 Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu Tyr 885 890 895 Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu 900 905 910 Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe 915 920 925 Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg Lys 930 935 940 Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg Lys 945 950 955 960 Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His Ala 965 970 975 Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val Thr Arg 980 985 990 Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys Lys 995 1000 1005 Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu Leu 1010 1015 1020 Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu 1025 1030 1035 Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser Arg 1040 1045 1050 Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr Ile 1055 1060 1065 Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile 1070 1075 1080 Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp 1085 1090 1095 Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu Ala 1100 1105 1110 Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys Ala 1115 1120 1125 Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly Asn 1130 1135 1140 Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe Val 1145 1150 1155 Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val Arg 1160 1165 1170 Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile 1175 1180 1185 Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val Val 1190 1195 1200 Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser 1205 1210 1215 Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu 1220 1225 1230 Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp 1235 1240 1245 Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro Ser 1250 1255 1260 Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp Leu 1265 1270 1275 Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val Arg 1280 1285 1290 Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg Pro 1295 1300 1305 Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 511 <211> 1326 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50163-nAPG07433.1 protein sequence" <400> 511 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asn Pro Glu Leu Asn His Glu Tyr Trp Met Arg Tyr Ala Leu Thr 35 40 45 Leu Ala Lys Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Tyr Asn Asp Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Arg Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Leu Asn Val Leu Asn Tyr Pro Gly Met Asn His His 145 150 155 160 Ile Glu Met Glu Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg Gln Pro Arg Met Val Lys Asn Ala Leu Lys Lys 180 185 190 Ser Pro Pro Asp Ser Pro Asn Leu Gln Ala Arg Ser Gly Gly Ser Ser 195 200 205 Gly Gly Ser Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr 210 215 220 Pro Glu Ser Ser Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp 225 230 235 240 Tyr Arg Ile Gly Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val 245 250 255 Ile Glu Leu Ser Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg 260 265 270 Ile Val Asp Gln Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys 275 280 285 Thr Gly Ala Ser Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg 290 295 300 Arg Arg Leu Asn Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu 305 310 315 320 Leu Val Gln His Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr 325 330 335 Pro Leu Ser Lys Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly 340 345 350 Leu Asp Arg Leu Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile His 355 360 365 Leu Ala Gln Arg Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys 370 375 380 Asp Thr Glu Thr Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys 385 390 395 400 Arg Leu Ser Leu Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro 405 410 415 Asp Phe Ser Lys Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val 420 425 430 Phe Ser Val Ser Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe 435 440 445 Ala Ala Gln Arg Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln 450 455 460 Glu Thr Tyr Leu Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly 465 470 475 480 Asn Ala Ile Leu Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys 485 490 495 Glu Arg Arg Ile Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala 500 505 510 Leu Asp Gln Val Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe 515 520 525 Thr Lys Glu Gln Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr 530 535 540 Asp Tyr Tyr Lys Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile 545 550 555 560 Arg Lys Trp Leu Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn 565 570 575 Tyr Asp Pro Asn Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile 580 585 590 Asn Leu Lys Ala Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser 595 600 605 Glu Arg Thr Asn Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly 610 615 620 Tyr Ala Leu Thr Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu 625 630 635 640 Lys Ser Ser His Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile 645 650 655 Glu Glu Leu Leu Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu 660 665 670 Lys Ala Ile Asn His Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr 675 680 685 Lys Glu Ala Val Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys 690 695 700 Glu Lys Arg Ser Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn 705 710 715 720 Pro Ile Val Lys Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala 725 730 735 Ile Ile Arg Arg His Gly Ser Pro His Ser Val His Ile Glu Leu Ala 740 745 750 Arg Glu Leu Ser Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala 755 760 765 Gln Asp Glu Asn Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser 770 775 780 Glu His Gly Ile Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys 785 790 795 800 Leu Trp Lys Glu Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile 805 810 815 Pro Ala Asp Thr Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala 820 825 830 Pro Ile Leu Glu Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile 835 840 845 Asp Ser Tyr His Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys 850 855 860 Lys Gly Asn Arg Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp 865 870 875 880 Trp Glu Ala Phe Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys 885 890 895 Lys Lys Arg Glu Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser 900 905 910 Glu Leu Ile Lys Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr 915 920 925 Phe Leu Lys Asn Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu 930 935 940 Asp Asn Pro Arg Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr 945 950 955 960 Ala His Phe Arg Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr 965 970 975 Tyr Leu His His Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His 980 985 990 His Met Val Thr Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn 995 1000 1005 Lys Ser Val Lys Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe 1010 1015 1020 Arg Asp Glu Leu Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys 1025 1030 1035 Lys Ile Ser Glu Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr 1040 1045 1050 Ile Phe Val Ser Arg Met Pro Lys Arg Ser Ile Thr Gly Ala Ala 1055 1060 1065 His Lys Gln Thr Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly 1070 1075 1080 Lys Thr Ile Ile Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe 1085 1090 1095 Asp Glu Asn Gly Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met 1100 1105 1110 Ala Thr Tyr Glu Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys 1115 1120 1125 Asn Ser Lys Lys Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys 1130 1135 1140 Lys Gly Thr Gly Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln 1145 1150 1155 Ala Lys Ser Phe Val Arg Glu Val Asn Gly Gly Val Ala Gln Asn 1160 1165 1170 Gly Asp Leu Val Arg Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr 1175 1180 1185 Tyr Met Val Pro Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu 1190 1195 1200 Pro Lys Lys Val Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu 1205 1210 1215 Thr Leu Asp Asn Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr 1220 1225 1230 Asp Leu Val Arg Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr 1235 1240 1245 Phe Gly Thr Leu Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp 1250 1255 1260 Val Asn Lys Pro Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys 1265 1270 1275 Thr Ile Glu Asp Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp 1280 1285 1290 Leu Arg Leu Val Arg Lys Glu Thr Arg Arg Asn Phe His Ser Gly 1295 1300 1305 Gly Ser Lys Arg Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys 1310 1315 1320 Lys Lys Lys 1325 <210> 512 <211> 1322 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50164-nAPG07433.1 protein sequence" <400> 512 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asn Pro Glu Phe Thr His Glu Tyr Trp Met Arg His Ala Leu Thr 35 40 45 Leu Ala Arg Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Thr Leu Val Phe Gly Val Arg Asn Glu Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Met Asn Val Leu Gly Tyr Pro Gly Met Asn His Gln 145 150 155 160 Val Lys Thr Ile Gly Gly Val Leu Ala Pro Glu Cys Ser Gly Leu Leu 165 170 175 Cys Asp Phe Tyr Arg Met Pro Arg Gln Gln Lys Asn Gln Gln Lys Ala 180 185 190 Glu Leu Lys Ser Ser Gly Asp Ser Gly Gly Ser Ser Gly Gly Ser Ser 195 200 205 Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser 210 215 220 Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly 225 230 235 240 Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser 245 250 255 Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln 260 265 270 Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser 275 280 285 Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn 290 295 300 Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His 305 310 315 320 Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys 325 330 335 Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu 340 345 350 Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg 355 360 365 Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr 370 375 380 Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu 385 390 395 400 Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys 405 410 415 Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser 420 425 430 Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg 435 440 445 Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu 450 455 460 Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu 465 470 475 480 Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile 485 490 495 Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val 500 505 510 Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln 515 520 525 Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys 530 535 540 Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu 545 550 555 560 Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn 565 570 575 Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala 580 585 590 Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn 595 600 605 Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr 610 615 620 Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His 625 630 635 640 Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu 645 650 655 Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn 660 665 670 His Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val 675 680 685 Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser 690 695 700 Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys 705 710 715 720 Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg 725 730 735 His Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser 740 745 750 Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn 755 760 765 Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile 770 775 780 Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu 785 790 795 800 Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr 805 810 815 Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu 820 825 830 Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His 835 840 845 Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg 850 855 860 Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe 865 870 875 880 Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu 885 890 895 Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys 900 905 910 Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn 915 920 925 Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg 930 935 940 Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg 945 950 955 960 Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His 965 970 975 Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val Thr 980 985 990 Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys 995 1000 1005 Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu 1010 1015 1020 Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu 1025 1030 1035 Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser 1040 1045 1050 Arg Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr 1055 1060 1065 Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile 1070 1075 1080 Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly 1085 1090 1095 Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu 1100 1105 1110 Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys 1115 1120 1125 Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly 1130 1135 1140 Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe 1145 1150 1155 Val Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val 1160 1165 1170 Arg Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro 1175 1180 1185 Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val 1190 1195 1200 Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn 1205 1210 1215 Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg 1220 1225 1230 Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu 1235 1240 1245 Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro 1250 1255 1260 Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp 1265 1270 1275 Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val 1280 1285 1290 Arg Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg 1295 1300 1305 Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 513 <211> 1319 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50165-nAPG07433.1 protein sequence" <400> 513 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp Asn Glu Phe Asn His Glu Tyr Trp Met Arg His Ala Leu Thr 35 40 45 Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asp Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Met Val Leu Gln Asn Tyr Arg Leu Ile Asn Ala Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly His Val Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Val Glu Val Thr Glu Gly Val Leu Arg Glu Gln Cys Ala Gly Met Leu 165 170 175 Cys Asp Phe Tyr Arg Glu Pro Arg Glu Gln Phe Asn Ala Leu Arg Lys 180 185 190 Ala Gln Lys Ala Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Ser Glu 195 200 205 Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser Gly Gly Ser 210 215 220 Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu Ala Ile 225 230 235 240 Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser Trp Asn Lys 245 250 255 Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln Gly Val Arg 260 265 270 Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser Leu Ala Glu 275 280 285 Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys Ser 290 295 300 Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His Gly Val Ile 305 310 315 320 Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys Ser Met 325 330 335 Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn His 340 345 350 Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly Phe 355 360 365 Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly Lys Val 370 375 380 Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr Arg Thr 385 390 395 400 Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr Asp Arg 405 410 415 Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala Glu 420 425 430 Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg Arg Phe Gln 435 440 445 Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln Ile Trp 450 455 460 Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys Val 465 470 475 480 Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys Ala 485 490 495 Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg Thr 500 505 510 Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg Glu Ile 515 520 525 Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys Thr 530 535 540 Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu Asp 545 550 555 560 Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu Leu 565 570 575 Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr Glu 580 585 590 Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu Thr Phe 595 600 605 Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val Tyr Lys 610 615 620 Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His Asn Leu Pro 625 630 635 640 Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser Leu Ser 645 650 655 Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn His Val Leu 660 665 670 Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp Gln Leu 675 680 685 Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys Phe Leu 690 695 700 Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala Leu 705 710 715 720 Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg His Gly Ser 725 730 735 Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser Lys Asn His 740 745 750 Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr Lys Lys 755 760 765 Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile Leu Asn Pro 770 775 780 Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly Glu 785 790 795 800 Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe Phe Asn 805 810 815 Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu Val Asp His 820 825 830 Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His Asn Lys Val 835 840 845 Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg Ile Pro Tyr 850 855 860 Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu Arg Tyr 865 870 875 880 Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu Tyr Leu Leu 885 890 895 Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu Arg His 900 905 910 Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe Ile Glu 915 920 925 Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg Lys Arg Arg 930 935 940 Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg Lys Arg Trp 945 950 955 960 Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His Ala Met Asp 965 970 975 Ala Ile Ile Val Ala Cys Thr Asp His His Met Val Thr Arg Val Thr 980 985 990 Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys Lys Pro Tyr 995 1000 1005 Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu Leu Ser His 1010 1015 1020 Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu Leu Lys 1025 1030 1035 Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser Arg Met Pro 1040 1045 1050 Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr Ile Met Arg 1055 1060 1065 Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile Glu Arg 1070 1075 1080 Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp Phe Lys 1085 1090 1095 Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu Ala Ile Lys 1100 1105 1110 Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys Ala Phe Glu 1115 1120 1125 Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly Asn Leu Ile 1130 1135 1140 Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe Val Arg Glu 1145 1150 1155 Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val Arg Val Asp 1160 1165 1170 Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile Tyr Val 1175 1180 1185 Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val Val Ala Ser 1190 1195 1200 Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser Phe Thr 1205 1210 1215 Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu Val Lys 1220 1225 1230 Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp Ile Asp 1235 1240 1245 Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro Ser Lys Lys 1250 1255 1260 Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp Leu Glu Lys 1265 1270 1275 Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val Arg Lys Glu 1280 1285 1290 Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg Pro Ala Ala 1295 1300 1305 Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 <210> 514 <211> 1324 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50166-nAPG07433.1 protein sequence" <400> 514 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp Asn Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu Thr 35 40 45 Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Met Val Leu Gln Asn Tyr Arg Leu Ile Asp Ala Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Ile Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Gln Val Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Ile Asn Ile Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Val Asp Val Thr Glu Gly Val Leu Ser Glu Arg Cys Ala Asn Met Leu 165 170 175 Cys Asp Phe Tyr Arg Glu Pro Arg Leu Gln Phe Asn Ala Gln Arg Lys 180 185 190 Ala Glu Lys Ala Gly Asn Ala Ala Ala Ser Gly Gly Ser Ser Gly Gly 195 200 205 Ser Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu 210 215 220 Ser Ser Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg 225 230 235 240 Ile Gly Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu 245 250 255 Leu Ser Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val 260 265 270 Asp Gln Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly 275 280 285 Ala Ser Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg 290 295 300 Leu Asn Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val 305 310 315 320 Gln His Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu 325 330 335 Ser Lys Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp 340 345 350 Arg Leu Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala 355 360 365 Gln Arg Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr 370 375 380 Glu Thr Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu 385 390 395 400 Ser Leu Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe 405 410 415 Ser Lys Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser 420 425 430 Val Ser Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala 435 440 445 Gln Arg Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr 450 455 460 Tyr Leu Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala 465 470 475 480 Ile Leu Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg 485 490 495 Arg Ile Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp 500 505 510 Gln Val Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys 515 520 525 Glu Gln Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr 530 535 540 Tyr Lys Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys 545 550 555 560 Trp Leu Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp 565 570 575 Pro Asn Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu 580 585 590 Lys Ala Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg 595 600 605 Thr Asn Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala 610 615 620 Leu Thr Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser 625 630 635 640 Ser His Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu 645 650 655 Leu Leu Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala 660 665 670 Ile Asn His Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu 675 680 685 Ala Val Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys 690 695 700 Arg Ser Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile 705 710 715 720 Val Lys Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile 725 730 735 Arg Arg His Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu 740 745 750 Leu Ser Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp 755 760 765 Glu Asn Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His 770 775 780 Gly Ile Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp 785 790 795 800 Lys Glu Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala 805 810 815 Asp Thr Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile 820 825 830 Leu Glu Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser 835 840 845 Tyr His Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly 850 855 860 Asn Arg Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu 865 870 875 880 Ala Phe Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys 885 890 895 Arg Glu Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu 900 905 910 Ile Lys Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu 915 920 925 Lys Asn Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn 930 935 940 Pro Arg Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His 945 950 955 960 Phe Arg Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu 965 970 975 His His Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met 980 985 990 Val Thr Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser 995 1000 1005 Val Lys Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp 1010 1015 1020 Glu Leu Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile 1025 1030 1035 Ser Glu Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe 1040 1045 1050 Val Ser Arg Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys 1055 1060 1065 Gln Thr Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr 1070 1075 1080 Ile Ile Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu 1085 1090 1095 Asn Gly Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr 1100 1105 1110 Tyr Glu Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser 1115 1120 1125 Lys Lys Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly 1130 1135 1140 Thr Gly Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys 1145 1150 1155 Ser Phe Val Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp 1160 1165 1170 Leu Val Arg Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met 1175 1180 1185 Val Pro Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys 1190 1195 1200 Lys Val Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu 1205 1210 1215 Asp Asn Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu 1220 1225 1230 Val Arg Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly 1235 1240 1245 Thr Leu Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn 1250 1255 1260 Lys Pro Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile 1265 1270 1275 Glu Asp Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg 1280 1285 1290 Leu Val Arg Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser 1295 1300 1305 Lys Arg Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys 1310 1315 1320 Lys <210> 515 <211> 1323 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50167-nAPG07433.1 protein sequence" <400> 515 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asn Pro Glu Leu Thr His Asp His Trp Met Arg His Ala Leu Thr 35 40 45 Leu Ala Gln Arg Ala Arg Asn Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Gly Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Val Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Gln Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Val Glu Ile Ile Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg His Pro Arg Leu Val Lys Asn Ala Leu Lys Lys 180 185 190 Asn Ala Gly Thr Ser Pro Thr Gln Ser Gly Gly Ser Ser Gly Gly Ser 195 200 205 Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser 210 215 220 Ser Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile 225 230 235 240 Gly Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu 245 250 255 Ser Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp 260 265 270 Gln Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala 275 280 285 Ser Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu 290 295 300 Asn Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln 305 310 315 320 His Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser 325 330 335 Lys Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg 340 345 350 Leu Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln 355 360 365 Arg Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu 370 375 380 Thr Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser 385 390 395 400 Leu Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser 405 410 415 Lys Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val 420 425 430 Ser Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln 435 440 445 Arg Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr 450 455 460 Leu Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile 465 470 475 480 Leu Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg 485 490 495 Ile Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln 500 505 510 Val Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu 515 520 525 Gln Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr 530 535 540 Lys Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp 545 550 555 560 Leu Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro 565 570 575 Asn Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys 580 585 590 Ala Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr 595 600 605 Asn Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu 610 615 620 Thr Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser 625 630 635 640 His Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu 645 650 655 Leu Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile 660 665 670 Asn His Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala 675 680 685 Val Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg 690 695 700 Ser Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val 705 710 715 720 Lys Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg 725 730 735 Arg His Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu 740 745 750 Ser Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu 755 760 765 Asn Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly 770 775 780 Ile Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys 785 790 795 800 Glu Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp 805 810 815 Thr Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu 820 825 830 Glu Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr 835 840 845 His Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn 850 855 860 Arg Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala 865 870 875 880 Phe Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg 885 890 895 Glu Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile 900 905 910 Lys Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys 915 920 925 Asn Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro 930 935 940 Arg Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe 945 950 955 960 Arg Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His 965 970 975 His Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val 980 985 990 Thr Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val 995 1000 1005 Lys Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu 1010 1015 1020 Leu Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser 1025 1030 1035 Glu Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val 1040 1045 1050 Ser Arg Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln 1055 1060 1065 Thr Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile 1070 1075 1080 Ile Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn 1085 1090 1095 Gly Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr 1100 1105 1110 Glu Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys 1115 1120 1125 Lys Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr 1130 1135 1140 Gly Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser 1145 1150 1155 Phe Val Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu 1160 1165 1170 Val Arg Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val 1175 1180 1185 Pro Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys 1190 1195 1200 Val Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp 1205 1210 1215 Asn Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val 1220 1225 1230 Arg Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr 1235 1240 1245 Leu Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys 1250 1255 1260 Pro Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu 1265 1270 1275 Asp Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu 1280 1285 1290 Val Arg Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys 1295 1300 1305 Arg Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 516 <211> 1320 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50168-nAPG07433.1 protein sequence" <400> 516 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp Thr Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu Met 35 40 45 Leu Ala Lys Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Lys Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Asn Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Val Glu Ile Ala Glu Gly Val Leu Ala Asp Glu Cys Ser Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg His Pro Arg Gln Gln Gln Asn Ala Leu Lys Gln 180 185 190 Ala Ala Lys His Asp Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Ser 195 200 205 Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser Gly Gly 210 215 220 Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu Ala 225 230 235 240 Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser Trp Asn 245 250 255 Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln Gly Val 260 265 270 Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser Leu Ala 275 280 285 Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys 290 295 300 Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His Gly Val 305 310 315 320 Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys Ser 325 330 335 Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn 340 345 350 His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly 355 360 365 Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly Lys 370 375 380 Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr Arg 385 390 395 400 Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr Asp 405 410 415 Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala 420 425 430 Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg Arg Phe 435 440 445 Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln Ile 450 455 460 Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys 465 470 475 480 Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys 485 490 495 Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg 500 505 510 Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg Glu 515 520 525 Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys 530 535 540 Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu 545 550 555 560 Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu 565 570 575 Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr 580 585 590 Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu Thr 595 600 605 Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val Tyr 610 615 620 Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His Asn Leu 625 630 635 640 Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser Leu 645 650 655 Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn His Val 660 665 670 Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp Gln 675 680 685 Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys Phe 690 695 700 Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala 705 710 715 720 Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg His Gly 725 730 735 Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser Lys Asn 740 745 750 His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr Lys 755 760 765 Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile Leu Asn 770 775 780 Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly 785 790 795 800 Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe Phe 805 810 815 Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu Val Asp 820 825 830 His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His Asn Lys 835 840 845 Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg Ile Pro 850 855 860 Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu Arg 865 870 875 880 Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu Tyr Leu 885 890 895 Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu Arg 900 905 910 His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe Ile 915 920 925 Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg Lys Arg 930 935 940 Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg Lys Arg 945 950 955 960 Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His Ala Met 965 970 975 Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val Thr Arg Val 980 985 990 Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys Lys Pro 995 1000 1005 Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu Leu Ser 1010 1015 1020 His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu Leu 1025 1030 1035 Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser Arg Met 1040 1045 1050 Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr Ile Met 1055 1060 1065 Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile Glu 1070 1075 1080 Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp Phe 1085 1090 1095 Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu Ala Ile 1100 1105 1110 Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys Ala Phe 1115 1120 1125 Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly Asn Leu 1130 1135 1140 Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe Val Arg 1145 1150 1155 Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val Arg Val 1160 1165 1170 Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile Tyr 1175 1180 1185 Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val Val Ala 1190 1195 1200 Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser Phe 1205 1210 1215 Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu Val 1220 1225 1230 Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp Ile 1235 1240 1245 Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro Ser Lys 1250 1255 1260 Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp Leu Glu 1265 1270 1275 Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val Arg Lys 1280 1285 1290 Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg Pro Ala 1295 1300 1305 Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 517 <211> 1325 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50169-nAPG07433.1 protein sequence" <400> 517 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp Ile Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu Met 35 40 45 Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly His Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Ile Glu Phe Thr Glu Gly Val Leu Ala Asp Glu Cys Ser Gly Met Leu 165 170 175 Cys Asp Phe Tyr Arg Tyr Pro Arg Gln Gln Gln Asn Thr Leu Lys Gln 180 185 190 Ala Ala Lys Ala Asn Pro Pro Ala Ala Gln Ser Gly Gly Ser Ser Gly 195 200 205 Gly Ser Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro 210 215 220 Glu Ser Ser Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr 225 230 235 240 Arg Ile Gly Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile 245 250 255 Glu Leu Ser Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile 260 265 270 Val Asp Gln Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr 275 280 285 Gly Ala Ser Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg 290 295 300 Arg Leu Asn Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu 305 310 315 320 Val Gln His Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro 325 330 335 Leu Ser Lys Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu 340 345 350 Asp Arg Leu Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu 355 360 365 Ala Gln Arg Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp 370 375 380 Thr Glu Thr Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg 385 390 395 400 Leu Ser Leu Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp 405 410 415 Phe Ser Lys Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe 420 425 430 Ser Val Ser Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala 435 440 445 Ala Gln Arg Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu 450 455 460 Thr Tyr Leu Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn 465 470 475 480 Ala Ile Leu Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu 485 490 495 Arg Arg Ile Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu 500 505 510 Asp Gln Val Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr 515 520 525 Lys Glu Gln Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp 530 535 540 Tyr Tyr Lys Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg 545 550 555 560 Lys Trp Leu Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr 565 570 575 Asp Pro Asn Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn 580 585 590 Leu Lys Ala Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu 595 600 605 Arg Thr Asn Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr 610 615 620 Ala Leu Thr Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys 625 630 635 640 Ser Ser His Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu 645 650 655 Glu Leu Leu Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys 660 665 670 Ala Ile Asn His Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys 675 680 685 Glu Ala Val Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu 690 695 700 Lys Arg Ser Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro 705 710 715 720 Ile Val Lys Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile 725 730 735 Ile Arg Arg His Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg 740 745 750 Glu Leu Ser Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln 755 760 765 Asp Glu Asn Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu 770 775 780 His Gly Ile Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu 785 790 795 800 Trp Lys Glu Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro 805 810 815 Ala Asp Thr Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro 820 825 830 Ile Leu Glu Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp 835 840 845 Ser Tyr His Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys 850 855 860 Gly Asn Arg Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp 865 870 875 880 Glu Ala Phe Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys 885 890 895 Lys Arg Glu Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu 900 905 910 Leu Ile Lys Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe 915 920 925 Leu Lys Asn Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp 930 935 940 Asn Pro Arg Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala 945 950 955 960 His Phe Arg Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr 965 970 975 Leu His His Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His 980 985 990 Met Val Thr Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys 995 1000 1005 Ser Val Lys Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg 1010 1015 1020 Asp Glu Leu Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys 1025 1030 1035 Ile Ser Glu Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile 1040 1045 1050 Phe Val Ser Arg Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His 1055 1060 1065 Lys Gln Thr Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys 1070 1075 1080 Thr Ile Ile Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp 1085 1090 1095 Glu Asn Gly Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala 1100 1105 1110 Thr Tyr Glu Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn 1115 1120 1125 Ser Lys Lys Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys 1130 1135 1140 Gly Thr Gly Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala 1145 1150 1155 Lys Ser Phe Val Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly 1160 1165 1170 Asp Leu Val Arg Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr 1175 1180 1185 Met Val Pro Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro 1190 1195 1200 Lys Lys Val Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr 1205 1210 1215 Leu Asp Asn Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp 1220 1225 1230 Leu Val Arg Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe 1235 1240 1245 Gly Thr Leu Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val 1250 1255 1260 Asn Lys Pro Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr 1265 1270 1275 Ile Glu Asp Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu 1280 1285 1290 Arg Leu Val Arg Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly 1295 1300 1305 Ser Lys Arg Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys 1310 1315 1320 Lys Lys 1325 <210> 518 <211> 1319 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50170-nAPG07433.1 protein sequence" <400> 518 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp Asn Glu Leu Asn His Glu Arg Trp Met Arg His Ala Leu Thr 35 40 45 Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Tyr Gln Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Gln Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Val Ala Ile Thr Glu Gly Val Leu Ala Glu Ser Cys Ser Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg His Pro Arg Glu Gln Lys Asn Ala Leu Arg Arg 180 185 190 Ala Ala Gln Ser Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Ser Glu 195 200 205 Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser Gly Gly Ser 210 215 220 Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu Ala Ile 225 230 235 240 Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser Trp Asn Lys 245 250 255 Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln Gly Val Arg 260 265 270 Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser Leu Ala Glu 275 280 285 Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys Ser 290 295 300 Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His Gly Val Ile 305 310 315 320 Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys Ser Met 325 330 335 Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn His 340 345 350 Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly Phe 355 360 365 Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly Lys Val 370 375 380 Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr Arg Thr 385 390 395 400 Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr Asp Arg 405 410 415 Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala Glu 420 425 430 Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg Arg Phe Gln 435 440 445 Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln Ile Trp 450 455 460 Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys Val 465 470 475 480 Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys Ala 485 490 495 Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg Thr 500 505 510 Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg Glu Ile 515 520 525 Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys Thr 530 535 540 Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu Asp 545 550 555 560 Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu Leu 565 570 575 Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr Glu 580 585 590 Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu Thr Phe 595 600 605 Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val Tyr Lys 610 615 620 Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His Asn Leu Pro 625 630 635 640 Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser Leu Ser 645 650 655 Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn His Val Leu 660 665 670 Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp Gln Leu 675 680 685 Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys Phe Leu 690 695 700 Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala Leu 705 710 715 720 Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg His Gly Ser 725 730 735 Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser Lys Asn His 740 745 750 Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr Lys Lys 755 760 765 Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile Leu Asn Pro 770 775 780 Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly Glu 785 790 795 800 Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe Phe Asn 805 810 815 Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu Val Asp His 820 825 830 Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His Asn Lys Val 835 840 845 Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg Ile Pro Tyr 850 855 860 Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu Arg Tyr 865 870 875 880 Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu Tyr Leu Leu 885 890 895 Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu Arg His 900 905 910 Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe Ile Glu 915 920 925 Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg Lys Arg Arg 930 935 940 Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg Lys Arg Trp 945 950 955 960 Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His Ala Met Asp 965 970 975 Ala Ile Ile Val Ala Cys Thr Asp His His Met Val Thr Arg Val Thr 980 985 990 Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys Lys Pro Tyr 995 1000 1005 Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu Leu Ser His 1010 1015 1020 Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu Leu Lys 1025 1030 1035 Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser Arg Met Pro 1040 1045 1050 Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr Ile Met Arg 1055 1060 1065 Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile Glu Arg 1070 1075 1080 Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp Phe Lys 1085 1090 1095 Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu Ala Ile Lys 1100 1105 1110 Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys Ala Phe Glu 1115 1120 1125 Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly Asn Leu Ile 1130 1135 1140 Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe Val Arg Glu 1145 1150 1155 Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val Arg Val Asp 1160 1165 1170 Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile Tyr Val 1175 1180 1185 Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val Val Ala Ser 1190 1195 1200 Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser Phe Thr 1205 1210 1215 Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu Val Lys 1220 1225 1230 Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp Ile Asp 1235 1240 1245 Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro Ser Lys Lys 1250 1255 1260 Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp Leu Glu Lys 1265 1270 1275 Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val Arg Lys Glu 1280 1285 1290 Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg Pro Ala Ala 1295 1300 1305 Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 <210> 519 <211> 1320 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50171-nAPG07433.1 protein sequence" <400> 519 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp Leu Glu Leu Asn Asp Glu Tyr Trp Met Arg His Ala Leu Thr 35 40 45 Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Ala Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Ala Arg Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Val Glu Ile Ser Glu Gly Val Leu Ala Glu Ser Cys Ser Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg Trp Pro Arg Glu Val Lys Asn Ala Leu Lys Lys 180 185 190 Ala Arg Glu Gln Asn Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Ser 195 200 205 Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser Gly Gly 210 215 220 Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu Ala 225 230 235 240 Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser Trp Asn 245 250 255 Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln Gly Val 260 265 270 Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser Leu Ala 275 280 285 Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys 290 295 300 Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His Gly Val 305 310 315 320 Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys Ser 325 330 335 Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn 340 345 350 His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly 355 360 365 Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly Lys 370 375 380 Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr Arg 385 390 395 400 Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr Asp 405 410 415 Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala 420 425 430 Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg Arg Phe 435 440 445 Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln Ile 450 455 460 Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys 465 470 475 480 Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys 485 490 495 Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg 500 505 510 Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg Glu 515 520 525 Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys 530 535 540 Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu 545 550 555 560 Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu 565 570 575 Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr 580 585 590 Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu Thr 595 600 605 Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val Tyr 610 615 620 Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His Asn Leu 625 630 635 640 Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser Leu 645 650 655 Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn His Val 660 665 670 Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp Gln 675 680 685 Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys Phe 690 695 700 Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala 705 710 715 720 Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg His Gly 725 730 735 Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser Lys Asn 740 745 750 His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr Lys 755 760 765 Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile Leu Asn 770 775 780 Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly 785 790 795 800 Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe Phe 805 810 815 Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu Val Asp 820 825 830 His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His Asn Lys 835 840 845 Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg Ile Pro 850 855 860 Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu Arg 865 870 875 880 Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu Tyr Leu 885 890 895 Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu Arg 900 905 910 His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe Ile 915 920 925 Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg Lys Arg 930 935 940 Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg Lys Arg 945 950 955 960 Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His Ala Met 965 970 975 Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val Thr Arg Val 980 985 990 Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys Lys Pro 995 1000 1005 Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu Leu Ser 1010 1015 1020 His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu Leu 1025 1030 1035 Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser Arg Met 1040 1045 1050 Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr Ile Met 1055 1060 1065 Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile Glu 1070 1075 1080 Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp Phe 1085 1090 1095 Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu Ala Ile 1100 1105 1110 Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys Ala Phe 1115 1120 1125 Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly Asn Leu 1130 1135 1140 Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe Val Arg 1145 1150 1155 Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val Arg Val 1160 1165 1170 Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile Tyr 1175 1180 1185 Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val Val Ala 1190 1195 1200 Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser Phe 1205 1210 1215 Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu Val 1220 1225 1230 Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp Ile 1235 1240 1245 Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro Ser Lys 1250 1255 1260 Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp Leu Glu 1265 1270 1275 Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val Arg Lys 1280 1285 1290 Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg Pro Ala 1295 1300 1305 Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 520 <211> 1323 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50172-nAPG07433.1 protein sequence" <400> 520 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp Leu Glu Leu Asp His Glu Tyr Trp Met Arg His Ala Leu Leu 35 40 45 Leu Ala Lys Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Thr Leu Val Tyr Gly Val Arg Asn Glu Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Met Asn Val Leu Gly Tyr Pro Gly Met Asn His Gln 145 150 155 160 Val Gln Val Ile Asp Gly Val Leu Ala Pro Glu Cys Ser Gly Leu Leu 165 170 175 Cys Asp Phe Tyr Arg Met Pro Arg Gln Gln Lys Asn Gln Gln Lys Ala 180 185 190 Glu Ser Thr Ser Ser Arg Gly Asp Ser Gly Gly Ser Ser Gly Gly Ser 195 200 205 Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser 210 215 220 Ser Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile 225 230 235 240 Gly Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu 245 250 255 Ser Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp 260 265 270 Gln Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala 275 280 285 Ser Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu 290 295 300 Asn Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln 305 310 315 320 His Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser 325 330 335 Lys Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg 340 345 350 Leu Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln 355 360 365 Arg Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu 370 375 380 Thr Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser 385 390 395 400 Leu Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser 405 410 415 Lys Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val 420 425 430 Ser Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln 435 440 445 Arg Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr 450 455 460 Leu Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile 465 470 475 480 Leu Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg 485 490 495 Ile Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln 500 505 510 Val Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu 515 520 525 Gln Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr 530 535 540 Lys Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp 545 550 555 560 Leu Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro 565 570 575 Asn Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys 580 585 590 Ala Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr 595 600 605 Asn Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu 610 615 620 Thr Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser 625 630 635 640 His Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu 645 650 655 Leu Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile 660 665 670 Asn His Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala 675 680 685 Val Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg 690 695 700 Ser Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val 705 710 715 720 Lys Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg 725 730 735 Arg His Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu 740 745 750 Ser Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu 755 760 765 Asn Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly 770 775 780 Ile Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys 785 790 795 800 Glu Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp 805 810 815 Thr Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu 820 825 830 Glu Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr 835 840 845 His Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn 850 855 860 Arg Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala 865 870 875 880 Phe Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg 885 890 895 Glu Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile 900 905 910 Lys Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys 915 920 925 Asn Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro 930 935 940 Arg Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe 945 950 955 960 Arg Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His 965 970 975 His Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val 980 985 990 Thr Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val 995 1000 1005 Lys Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu 1010 1015 1020 Leu Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser 1025 1030 1035 Glu Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val 1040 1045 1050 Ser Arg Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln 1055 1060 1065 Thr Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile 1070 1075 1080 Ile Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn 1085 1090 1095 Gly Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr 1100 1105 1110 Glu Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys 1115 1120 1125 Lys Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr 1130 1135 1140 Gly Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser 1145 1150 1155 Phe Val Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu 1160 1165 1170 Val Arg Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val 1175 1180 1185 Pro Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys 1190 1195 1200 Val Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp 1205 1210 1215 Asn Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val 1220 1225 1230 Arg Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr 1235 1240 1245 Leu Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys 1250 1255 1260 Pro Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu 1265 1270 1275 Asp Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu 1280 1285 1290 Val Arg Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys 1295 1300 1305 Arg Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 521 <211> 1316 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50173-nAPG07433.1 protein sequence" <400> 521 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp Thr Glu Leu Thr His Glu Tyr Trp Met Arg His Ala Leu Met 35 40 45 Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Arg Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Gly 115 120 125 Arg Ile Gly Thr Leu Val Phe Gly Val Arg Asn Leu Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Val Glu Ile Val Glu Gly Thr Leu Ser Asp Glu Cys Ser Gly Met Leu 165 170 175 Cys Glu Phe Tyr Arg Gln Pro Arg Leu Ala Phe Asn Ala Gln Lys Gln 180 185 190 Ala Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Ser Glu Thr Pro Gly 195 200 205 Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser Gly Gly Ser Ser Gly Gly 210 215 220 Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu Ala Ile Gly Thr Asn 225 230 235 240 Ser Ile Gly Trp Gly Val Ile Glu Leu Ser Trp Asn Lys Asp Arg Glu 245 250 255 Arg Tyr Glu Lys Val Arg Ile Val Asp Gln Gly Val Arg Met Phe Asp 260 265 270 Arg Ala Glu Met Pro Lys Thr Gly Ala Ser Leu Ala Glu Pro Arg Arg 275 280 285 Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys Ser Gln Arg Lys 290 295 300 Lys Asn Ile Arg Asn Leu Leu Val Gln His Gly Val Ile Thr Gln Glu 305 310 315 320 Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys Ser Met Asp Ile Trp 325 330 335 Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn His Phe Glu Trp 340 345 350 Ala Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly Phe Lys Ser Asn 355 360 365 Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly Lys Val Leu Ser Ser 370 375 380 Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr Arg Thr Val Gly Glu 385 390 395 400 Met Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr Asp Arg Lys Arg Asn 405 410 415 Ser Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala Glu Leu Glu Lys 420 425 430 Glu Ile Val Thr Leu Phe Ala Ala Gln Arg Arg Phe Gln Ser Pro Tyr 435 440 445 Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln Ile Trp Thr His Gln 450 455 460 Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys Val Gly Tyr Cys 465 470 475 480 Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys Ala Thr Tyr Thr 485 490 495 Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg Thr Arg Leu Gly 500 505 510 Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg Glu Ile Ile Leu Asn 515 520 525 Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys Thr Ile Pro Glu 530 535 540 Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu Asp Glu Thr Ile 545 550 555 560 Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu Leu Lys Lys Ile 565 570 575 Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr Glu Ile Asn Lys 580 585 590 Val Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu Thr Phe Ser Thr Leu 595 600 605 Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val Tyr Lys Thr Asp Lys 610 615 620 Asp Ile Arg Ser Tyr Leu Lys Ser Ser His Asn Leu Pro Lys Arg Cys 625 630 635 640 Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser Leu Ser Tyr Thr Lys 645 650 655 Phe Gly His Leu Ser Leu Lys Ala Ile Asn His Val Leu Ser Ile Met 660 665 670 Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp Gln Leu Gly Tyr Asp 675 680 685 Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys Phe Leu Pro Pro Ile 690 695 700 Ser Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala Leu Thr Gln Ala 705 710 715 720 Arg Lys Val Val Asn Ala Ile Ile Arg Arg His Gly Ser Pro His Ser 725 730 735 Val His Ile Glu Leu Ala Arg Glu Leu Ser Lys Asn His Asp Glu Arg 740 745 750 Thr Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr Lys Lys Asn Lys Gly 755 760 765 Ala Ile Ser Ile Leu Ser Glu His Gly Ile Leu Asn Pro Thr Gly Tyr 770 775 780 Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly Glu Arg Cys Ala 785 790 795 800 Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe Phe Asn Glu Leu Lys 805 810 815 Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu Val Asp His Ile Leu Pro 820 825 830 Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His Asn Lys Val Leu Val Tyr 835 840 845 Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg Ile Pro Tyr Thr Tyr Phe 850 855 860 Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu Arg Tyr Val Arg Ser 865 870 875 880 Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu Tyr Leu Leu Lys Arg Ala 885 890 895 Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu Arg His Leu Asn Asp 900 905 910 Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe Ile Glu Gln Asn Leu 915 920 925 Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg Lys Arg Arg Val Gln Thr 930 935 940 Val Asn Gly Val Ile Thr Ala His Phe Arg Lys Arg Trp Gly Leu Glu 945 950 955 960 Lys Asp Arg Gln Glu Thr Tyr Leu His His Ala Met Asp Ala Ile Ile 965 970 975 Val Ala Cys Thr Asp His His Met Val Thr Arg Val Thr Glu Tyr Tyr 980 985 990 Gln Ile Lys Glu Ser Asn Lys Ser Val Lys Lys Pro Tyr Phe Pro Met 995 1000 1005 Pro Trp Glu Gly Phe Arg Asp Glu Leu Leu Ser His Leu Ala Ser 1010 1015 1020 Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu Leu Lys Ala Gly Tyr 1025 1030 1035 Gln Ser Leu Asp Tyr Ile Phe Val Ser Arg Met Pro Lys Arg Ser 1040 1045 1050 Ile Thr Gly Ala Ala His Lys Gln Thr Ile Met Arg Lys Gly Gly 1055 1060 1065 Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile Glu Arg Leu His Leu 1070 1075 1080 Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp Phe Lys Met Val Gly 1085 1090 1095 Lys Glu Gln Asp Met Ala Thr Tyr Glu Ala Ile Lys Gln Arg Tyr 1100 1105 1110 Leu Glu His Gly Lys Asn Ser Lys Lys Ala Phe Glu Thr Pro Leu 1115 1120 1125 Tyr Lys Pro Ser Lys Lys Gly Thr Gly Asn Leu Ile Lys Arg Val 1130 1135 1140 Lys Val Glu Gly Gln Ala Lys Ser Phe Val Arg Glu Val Asn Gly 1145 1150 1155 Gly Val Ala Gln Asn Gly Asp Leu Val Arg Val Asp Leu Phe Glu 1160 1165 1170 Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile Tyr Val Pro Asp Thr 1175 1180 1185 Val Cys Ser Glu Leu Pro Lys Lys Val Val Ala Ser Ser Lys Gly 1190 1195 1200 Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser Phe Thr Phe Lys Phe 1205 1210 1215 Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu Val Lys Gly Asp Glu 1220 1225 1230 Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp Ile Asp Ser Asp Arg 1235 1240 1245 Leu Asn Phe Lys Asp Val Asn Lys Pro Ser Lys Lys Asn Glu Tyr 1250 1255 1260 Arg Tyr Ser Leu Lys Thr Ile Glu Asp Leu Glu Lys Tyr Glu Val 1265 1270 1275 Gly Val Leu Gly Asp Leu Arg Leu Val Arg Lys Glu Thr Arg Arg 1280 1285 1290 Asn Phe His Ser Gly Gly Ser Lys Arg Pro Ala Ala Thr Lys Lys 1295 1300 1305 Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 <210> 522 <211> 1327 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50174-nAPG07433.1 protein sequence" <400> 522 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Ile Pro Glu Leu Asn His Asp Val Trp Met Arg His Ala Leu Thr 35 40 45 Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Gly Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Gln Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Val Glu Ile Thr Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg Gln Pro Arg Leu Val Lys Asn Ala Leu Lys Lys 180 185 190 Pro Ala Gly Asp Pro Ser Ala Leu Gln Asn Asn Arg Ser Gly Gly Ser 195 200 205 Ser Gly Gly Ser Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala 210 215 220 Thr Pro Glu Ser Ser Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu 225 230 235 240 Asp Tyr Arg Ile Gly Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly 245 250 255 Val Ile Glu Leu Ser Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val 260 265 270 Arg Ile Val Asp Gln Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro 275 280 285 Lys Thr Gly Ala Ser Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser 290 295 300 Arg Arg Arg Leu Asn Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn 305 310 315 320 Leu Leu Val Gln His Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu 325 330 335 Tyr Pro Leu Ser Lys Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp 340 345 350 Gly Leu Asp Arg Leu Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile 355 360 365 His Leu Ala Gln Arg Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu 370 375 380 Lys Asp Thr Glu Thr Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu 385 390 395 400 Lys Arg Leu Ser Leu Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp 405 410 415 Pro Asp Phe Ser Lys Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr 420 425 430 Val Phe Ser Val Ser Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu 435 440 445 Phe Ala Ala Gln Arg Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu 450 455 460 Gln Glu Thr Tyr Leu Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser 465 470 475 480 Gly Asn Ala Ile Leu Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly 485 490 495 Lys Glu Arg Arg Ile Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser 500 505 510 Ala Leu Asp Gln Val Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro 515 520 525 Phe Thr Lys Glu Gln Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg 530 535 540 Thr Asp Tyr Tyr Lys Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp 545 550 555 560 Ile Arg Lys Trp Leu Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu 565 570 575 Asn Tyr Asp Pro Asn Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe 580 585 590 Ile Asn Leu Lys Ala Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr 595 600 605 Ser Glu Arg Thr Asn Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile 610 615 620 Gly Tyr Ala Leu Thr Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr 625 630 635 640 Leu Lys Ser Ser His Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu 645 650 655 Ile Glu Glu Leu Leu Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser 660 665 670 Leu Lys Ala Ile Asn His Val Leu Ser Ile Met Gln Lys Gly Asn Thr 675 680 685 Tyr Lys Glu Ala Val Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys 690 695 700 Lys Glu Lys Arg Ser Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr 705 710 715 720 Asn Pro Ile Val Lys Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn 725 730 735 Ala Ile Ile Arg Arg His Gly Ser Pro His Ser Val His Ile Glu Leu 740 745 750 Ala Arg Glu Leu Ser Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser 755 760 765 Ala Gln Asp Glu Asn Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu 770 775 780 Ser Glu His Gly Ile Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr 785 790 795 800 Lys Leu Trp Lys Glu Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu 805 810 815 Ile Pro Ala Asp Thr Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly 820 825 830 Ala Pro Ile Leu Glu Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe 835 840 845 Ile Asp Ser Tyr His Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg 850 855 860 Lys Lys Gly Asn Arg Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys 865 870 875 880 Asp Trp Glu Ala Phe Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser 885 890 895 Lys Lys Lys Arg Glu Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu 900 905 910 Ser Glu Leu Ile Lys Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser 915 920 925 Thr Phe Leu Lys Asn Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala 930 935 940 Glu Asp Asn Pro Arg Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile 945 950 955 960 Thr Ala His Phe Arg Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu 965 970 975 Thr Tyr Leu His His Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp 980 985 990 His His Met Val Thr Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser 995 1000 1005 Asn Lys Ser Val Lys Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly 1010 1015 1020 Phe Arg Asp Glu Leu Leu Ser His Leu Ala Ser Gln Pro Ile Ala 1025 1030 1035 Lys Lys Ile Ser Glu Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp 1040 1045 1050 Tyr Ile Phe Val Ser Arg Met Pro Lys Arg Ser Ile Thr Gly Ala 1055 1060 1065 Ala His Lys Gln Thr Ile Met Arg Lys Gly Gly Ile Asp Lys Lys 1070 1075 1080 Gly Lys Thr Ile Ile Ile Glu Arg Leu His Leu Lys Asp Ile Lys 1085 1090 1095 Phe Asp Glu Asn Gly Asp Phe Lys Met Val Gly Lys Glu Gln Asp 1100 1105 1110 Met Ala Thr Tyr Glu Ala Ile Lys Gln Arg Tyr Leu Glu His Gly 1115 1120 1125 Lys Asn Ser Lys Lys Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser 1130 1135 1140 Lys Lys Gly Thr Gly Asn Leu Ile Lys Arg Val Lys Val Glu Gly 1145 1150 1155 Gln Ala Lys Ser Phe Val Arg Glu Val Asn Gly Gly Val Ala Gln 1160 1165 1170 Asn Gly Asp Leu Val Arg Val Asp Leu Phe Glu Lys Asp Asp Lys 1175 1180 1185 Tyr Tyr Met Val Pro Ile Tyr Val Pro Asp Thr Val Cys Ser Glu 1190 1195 1200 Leu Pro Lys Lys Val Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp 1205 1210 1215 Leu Thr Leu Asp Asn Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro 1220 1225 1230 Tyr Asp Leu Val Arg Leu Val Lys Gly Asp Glu Asp Arg Phe Leu 1235 1240 1245 Tyr Phe Gly Thr Leu Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys 1250 1255 1260 Asp Val Asn Lys Pro Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu 1265 1270 1275 Lys Thr Ile Glu Asp Leu Glu Lys Tyr Glu Val Gly Val Leu Gly 1280 1285 1290 Asp Leu Arg Leu Val Arg Lys Glu Thr Arg Arg Asn Phe His Ser 1295 1300 1305 Gly Gly Ser Lys Arg Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala 1310 1315 1320 Lys Lys Lys Lys 1325 <210> 523 <211> 1320 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50175-nAPG07433.1 protein sequence" <400> 523 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp Leu Glu Leu Asn Asp Glu Tyr Trp Met Arg His Ala Leu Thr 35 40 45 Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Ala Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Ala Arg Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Val Glu Ile Ser Glu Gly Val Leu Ala Gly Ser Cys Ser Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg Trp Pro Arg Glu Val Lys Asn Ala Leu Lys Lys 180 185 190 Ala Arg Glu Gln Asn Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Ser 195 200 205 Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser Gly Gly 210 215 220 Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu Ala 225 230 235 240 Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser Trp Asn 245 250 255 Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln Gly Val 260 265 270 Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser Leu Ala 275 280 285 Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys 290 295 300 Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His Gly Val 305 310 315 320 Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys Ser 325 330 335 Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn 340 345 350 His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly 355 360 365 Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly Lys 370 375 380 Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr Arg 385 390 395 400 Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr Asp 405 410 415 Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala 420 425 430 Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg Arg Phe 435 440 445 Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln Ile 450 455 460 Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys 465 470 475 480 Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys 485 490 495 Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg 500 505 510 Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg Glu 515 520 525 Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys 530 535 540 Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu 545 550 555 560 Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu 565 570 575 Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr 580 585 590 Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu Thr 595 600 605 Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val Tyr 610 615 620 Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His Asn Leu 625 630 635 640 Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser Leu 645 650 655 Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn His Val 660 665 670 Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp Gln 675 680 685 Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys Phe 690 695 700 Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala 705 710 715 720 Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg His Gly 725 730 735 Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser Lys Asn 740 745 750 His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr Lys 755 760 765 Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile Leu Asn 770 775 780 Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly 785 790 795 800 Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe Phe 805 810 815 Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu Val Asp 820 825 830 His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His Asn Lys 835 840 845 Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg Ile Pro 850 855 860 Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu Arg 865 870 875 880 Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu Tyr Leu 885 890 895 Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu Arg 900 905 910 His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe Ile 915 920 925 Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg Lys Arg 930 935 940 Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg Lys Arg 945 950 955 960 Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His Ala Met 965 970 975 Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val Thr Arg Val 980 985 990 Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys Lys Pro 995 1000 1005 Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu Leu Ser 1010 1015 1020 His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu Leu 1025 1030 1035 Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser Arg Met 1040 1045 1050 Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr Ile Met 1055 1060 1065 Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile Glu 1070 1075 1080 Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp Phe 1085 1090 1095 Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu Ala Ile 1100 1105 1110 Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys Ala Phe 1115 1120 1125 Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly Asn Leu 1130 1135 1140 Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe Val Arg 1145 1150 1155 Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val Arg Val 1160 1165 1170 Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile Tyr 1175 1180 1185 Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val Val Ala 1190 1195 1200 Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser Phe 1205 1210 1215 Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu Val 1220 1225 1230 Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp Ile 1235 1240 1245 Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro Ser Lys 1250 1255 1260 Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp Leu Glu 1265 1270 1275 Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val Arg Lys 1280 1285 1290 Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg Pro Ala 1295 1300 1305 Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 524 <211> 1307 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50176-nAPG07433.1 protein sequence" <400> 524 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp Ile Glu Gln Asn His Glu Tyr Trp Met Arg His Ala Leu Val 35 40 45 Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Gly 115 120 125 Arg Ile Gly Ser Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Ile Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Val Glu Met Thr Glu Gly Val Leu Ala Asp Glu Cys Ser Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg His Pro Arg Ser Gly Gly Ser Ser Gly Gly Ser 180 185 190 Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser 195 200 205 Ser Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile 210 215 220 Gly Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu 225 230 235 240 Ser Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp 245 250 255 Gln Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala 260 265 270 Ser Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu 275 280 285 Asn Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln 290 295 300 His Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser 305 310 315 320 Lys Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg 325 330 335 Leu Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln 340 345 350 Arg Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu 355 360 365 Thr Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser 370 375 380 Leu Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser 385 390 395 400 Lys Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val 405 410 415 Ser Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln 420 425 430 Arg Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr 435 440 445 Leu Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile 450 455 460 Leu Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg 465 470 475 480 Ile Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln 485 490 495 Val Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu 500 505 510 Gln Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr 515 520 525 Lys Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp 530 535 540 Leu Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro 545 550 555 560 Asn Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys 565 570 575 Ala Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr 580 585 590 Asn Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu 595 600 605 Thr Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser 610 615 620 His Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu 625 630 635 640 Leu Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile 645 650 655 Asn His Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala 660 665 670 Val Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg 675 680 685 Ser Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val 690 695 700 Lys Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg 705 710 715 720 Arg His Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu 725 730 735 Ser Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu 740 745 750 Asn Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly 755 760 765 Ile Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys 770 775 780 Glu Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp 785 790 795 800 Thr Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu 805 810 815 Glu Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr 820 825 830 His Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn 835 840 845 Arg Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala 850 855 860 Phe Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg 865 870 875 880 Glu Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile 885 890 895 Lys Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys 900 905 910 Asn Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro 915 920 925 Arg Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe 930 935 940 Arg Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His 945 950 955 960 His Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val 965 970 975 Thr Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val 980 985 990 Lys Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu 995 1000 1005 Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu 1010 1015 1020 Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser 1025 1030 1035 Arg Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr 1040 1045 1050 Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile 1055 1060 1065 Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly 1070 1075 1080 Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu 1085 1090 1095 Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys 1100 1105 1110 Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly 1115 1120 1125 Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe 1130 1135 1140 Val Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val 1145 1150 1155 Arg Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro 1160 1165 1170 Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val 1175 1180 1185 Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn 1190 1195 1200 Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg 1205 1210 1215 Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu 1220 1225 1230 Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro 1235 1240 1245 Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp 1250 1255 1260 Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val 1265 1270 1275 Arg Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg 1280 1285 1290 Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1295 1300 1305 <210> 525 <211> 1322 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50177-nAPG07433.1 protein sequence" <400> 525 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Cys Asn Pro Glu Arg Asp His Glu Tyr Trp Met Arg His Ala Leu Thr 35 40 45 Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Met Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Thr Leu Val Phe Gly Val Arg Asn Glu Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Leu Asn Val Leu Gly Tyr Pro Gly Met Asn His Gln 145 150 155 160 Val Lys Thr Ile Gly Gly Val Leu Ala Pro Ala Cys Ser Ala Leu Leu 165 170 175 Cys Asp Phe Tyr Arg Met Pro Arg Gln Gln Lys Asn Gln Gln Lys Ala 180 185 190 Glu Leu Lys Leu Ser Asn Asp Ser Gly Gly Ser Ser Gly Gly Ser Ser 195 200 205 Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser 210 215 220 Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly 225 230 235 240 Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser 245 250 255 Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln 260 265 270 Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser 275 280 285 Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn 290 295 300 Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His 305 310 315 320 Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys 325 330 335 Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu 340 345 350 Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg 355 360 365 Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr 370 375 380 Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu 385 390 395 400 Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys 405 410 415 Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser 420 425 430 Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg 435 440 445 Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu 450 455 460 Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu 465 470 475 480 Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile 485 490 495 Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val 500 505 510 Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln 515 520 525 Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys 530 535 540 Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu 545 550 555 560 Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn 565 570 575 Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala 580 585 590 Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn 595 600 605 Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr 610 615 620 Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His 625 630 635 640 Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu 645 650 655 Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn 660 665 670 His Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val 675 680 685 Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser 690 695 700 Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys 705 710 715 720 Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg 725 730 735 His Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser 740 745 750 Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn 755 760 765 Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile 770 775 780 Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu 785 790 795 800 Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr 805 810 815 Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu 820 825 830 Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His 835 840 845 Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg 850 855 860 Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe 865 870 875 880 Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu 885 890 895 Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys 900 905 910 Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn 915 920 925 Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg 930 935 940 Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg 945 950 955 960 Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His 965 970 975 Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val Thr 980 985 990 Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys 995 1000 1005 Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu 1010 1015 1020 Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu 1025 1030 1035 Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser 1040 1045 1050 Arg Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr 1055 1060 1065 Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile 1070 1075 1080 Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly 1085 1090 1095 Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu 1100 1105 1110 Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys 1115 1120 1125 Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly 1130 1135 1140 Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe 1145 1150 1155 Val Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val 1160 1165 1170 Arg Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro 1175 1180 1185 Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val 1190 1195 1200 Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn 1205 1210 1215 Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg 1220 1225 1230 Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu 1235 1240 1245 Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro 1250 1255 1260 Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp 1265 1270 1275 Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val 1280 1285 1290 Arg Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg 1295 1300 1305 Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 526 <211> 1316 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50178-nAPG07433.1 protein sequence" <400> 526 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Ala Ile Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu Gly 35 40 45 Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Tyr Gln Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Arg Val Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Val Glu Val Thr Glu Gly Val Leu Ala Gly Glu Cys Ser Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg Ala Pro Arg Ala Gln Phe Asn Ala Gln Lys Arg 180 185 190 Pro Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Ser Glu Thr Pro Gly 195 200 205 Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser Gly Gly Ser Ser Gly Gly 210 215 220 Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly Leu Ala Ile Gly Thr Asn 225 230 235 240 Ser Ile Gly Trp Gly Val Ile Glu Leu Ser Trp Asn Lys Asp Arg Glu 245 250 255 Arg Tyr Glu Lys Val Arg Ile Val Asp Gln Gly Val Arg Met Phe Asp 260 265 270 Arg Ala Glu Met Pro Lys Thr Gly Ala Ser Leu Ala Glu Pro Arg Arg 275 280 285 Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn Arg Lys Ser Gln Arg Lys 290 295 300 Lys Asn Ile Arg Asn Leu Leu Val Gln His Gly Val Ile Thr Gln Glu 305 310 315 320 Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys Lys Ser Met Asp Ile Trp 325 330 335 Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu Leu Asn His Phe Glu Trp 340 345 350 Ala Arg Leu Leu Ile His Leu Ala Gln Arg Arg Gly Phe Lys Ser Asn 355 360 365 Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr Gly Lys Val Leu Ser Ser 370 375 380 Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu Tyr Arg Thr Val Gly Glu 385 390 395 400 Met Trp Met Lys Asp Pro Asp Phe Ser Lys Tyr Asp Arg Lys Arg Asn 405 410 415 Ser Pro Asn Glu Tyr Val Phe Ser Val Ser Arg Ala Glu Leu Glu Lys 420 425 430 Glu Ile Val Thr Leu Phe Ala Ala Gln Arg Arg Phe Gln Ser Pro Tyr 435 440 445 Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu Gln Ile Trp Thr His Gln 450 455 460 Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu Asn Lys Val Gly Tyr Cys 465 470 475 480 Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile Pro Lys Ala Thr Tyr Thr 485 490 495 Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val Asn Arg Thr Arg Leu Gly 500 505 510 Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln Arg Glu Ile Ile Leu Asn 515 520 525 Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys Lys Lys Thr Ile Pro Glu 530 535 540 Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu Glu Leu Asp Glu Thr Ile 545 550 555 560 Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn Glu Glu Leu Lys Lys Ile 565 570 575 Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala Phe Tyr Glu Ile Asn Lys 580 585 590 Val Val Ala Asn Tyr Ser Glu Arg Thr Asn Glu Thr Phe Ser Thr Leu 595 600 605 Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr Val Tyr Lys Thr Asp Lys 610 615 620 Asp Ile Arg Ser Tyr Leu Lys Ser Ser His Asn Leu Pro Lys Arg Cys 625 630 635 640 Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu Ser Leu Ser Tyr Thr Lys 645 650 655 Phe Gly His Leu Ser Leu Lys Ala Ile Asn His Val Leu Ser Ile Met 660 665 670 Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val Asp Gln Leu Gly Tyr Asp 675 680 685 Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser Lys Phe Leu Pro Pro Ile 690 695 700 Ser Asp Glu Ile Thr Asn Pro Ile Val Lys Arg Ala Leu Thr Gln Ala 705 710 715 720 Arg Lys Val Val Asn Ala Ile Ile Arg Arg His Gly Ser Pro His Ser 725 730 735 Val His Ile Glu Leu Ala Arg Glu Leu Ser Lys Asn His Asp Glu Arg 740 745 750 Thr Lys Ile Val Ser Ala Gln Asp Glu Asn Tyr Lys Lys Asn Lys Gly 755 760 765 Ala Ile Ser Ile Leu Ser Glu His Gly Ile Leu Asn Pro Thr Gly Tyr 770 775 780 Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu Gln Gly Glu Arg Cys Ala 785 790 795 800 Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr Phe Phe Asn Glu Leu Lys 805 810 815 Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu Val Asp His Ile Leu Pro 820 825 830 Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His Asn Lys Val Leu Val Tyr 835 840 845 Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg Ile Pro Tyr Thr Tyr Phe 850 855 860 Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe Glu Arg Tyr Val Arg Ser 865 870 875 880 Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu Tyr Leu Leu Lys Arg Ala 885 890 895 Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys Glu Arg His Leu Asn Asp 900 905 910 Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn Phe Ile Glu Gln Asn Leu 915 920 925 Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg Lys Arg Arg Val Gln Thr 930 935 940 Val Asn Gly Val Ile Thr Ala His Phe Arg Lys Arg Trp Gly Leu Glu 945 950 955 960 Lys Asp Arg Gln Glu Thr Tyr Leu His His Ala Met Asp Ala Ile Ile 965 970 975 Val Ala Cys Thr Asp His His Met Val Thr Arg Val Thr Glu Tyr Tyr 980 985 990 Gln Ile Lys Glu Ser Asn Lys Ser Val Lys Lys Pro Tyr Phe Pro Met 995 1000 1005 Pro Trp Glu Gly Phe Arg Asp Glu Leu Leu Ser His Leu Ala Ser 1010 1015 1020 Gln Pro Ile Ala Lys Lys Ile Ser Glu Glu Leu Lys Ala Gly Tyr 1025 1030 1035 Gln Ser Leu Asp Tyr Ile Phe Val Ser Arg Met Pro Lys Arg Ser 1040 1045 1050 Ile Thr Gly Ala Ala His Lys Gln Thr Ile Met Arg Lys Gly Gly 1055 1060 1065 Ile Asp Lys Lys Gly Lys Thr Ile Ile Ile Glu Arg Leu His Leu 1070 1075 1080 Lys Asp Ile Lys Phe Asp Glu Asn Gly Asp Phe Lys Met Val Gly 1085 1090 1095 Lys Glu Gln Asp Met Ala Thr Tyr Glu Ala Ile Lys Gln Arg Tyr 1100 1105 1110 Leu Glu His Gly Lys Asn Ser Lys Lys Ala Phe Glu Thr Pro Leu 1115 1120 1125 Tyr Lys Pro Ser Lys Lys Gly Thr Gly Asn Leu Ile Lys Arg Val 1130 1135 1140 Lys Val Glu Gly Gln Ala Lys Ser Phe Val Arg Glu Val Asn Gly 1145 1150 1155 Gly Val Ala Gln Asn Gly Asp Leu Val Arg Val Asp Leu Phe Glu 1160 1165 1170 Lys Asp Asp Lys Tyr Tyr Met Val Pro Ile Tyr Val Pro Asp Thr 1175 1180 1185 Val Cys Ser Glu Leu Pro Lys Lys Val Val Ala Ser Ser Lys Gly 1190 1195 1200 Tyr Glu Gln Trp Leu Thr Leu Asp Asn Ser Phe Thr Phe Lys Phe 1205 1210 1215 Ser Leu Tyr Pro Tyr Asp Leu Val Arg Leu Val Lys Gly Asp Glu 1220 1225 1230 Asp Arg Phe Leu Tyr Phe Gly Thr Leu Asp Ile Asp Ser Asp Arg 1235 1240 1245 Leu Asn Phe Lys Asp Val Asn Lys Pro Ser Lys Lys Asn Glu Tyr 1250 1255 1260 Arg Tyr Ser Leu Lys Thr Ile Glu Asp Leu Glu Lys Tyr Glu Val 1265 1270 1275 Gly Val Leu Gly Asp Leu Arg Leu Val Arg Lys Glu Thr Arg Arg 1280 1285 1290 Asn Phe His Ser Gly Gly Ser Lys Arg Pro Ala Ala Thr Lys Lys 1295 1300 1305 Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 <210> 527 <211> 1323 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50179-nAPG07433.1 protein sequence" <400> 527 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asn Pro Glu Leu Asn His Glu Tyr Trp Met Arg Tyr Ala Leu Thr 35 40 45 Leu Ala Lys Arg Ala Arg Glu Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Glu Arg Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Met Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly His Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Met Asn Val Leu Asn Tyr Pro Gly Met Asn His Arg 145 150 155 160 Val Ala Ile Thr Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg Gln Pro Arg Gln Val Lys Asn Ala Leu Lys Lys 180 185 190 Thr Leu Ser Asp Ser Gln Glu Gln Ser Gly Gly Ser Ser Gly Gly Ser 195 200 205 Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser 210 215 220 Ser Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile 225 230 235 240 Gly Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu 245 250 255 Ser Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp 260 265 270 Gln Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala 275 280 285 Ser Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu 290 295 300 Asn Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln 305 310 315 320 His Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser 325 330 335 Lys Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg 340 345 350 Leu Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln 355 360 365 Arg Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu 370 375 380 Thr Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser 385 390 395 400 Leu Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser 405 410 415 Lys Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val 420 425 430 Ser Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln 435 440 445 Arg Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr 450 455 460 Leu Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile 465 470 475 480 Leu Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg 485 490 495 Ile Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln 500 505 510 Val Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu 515 520 525 Gln Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr 530 535 540 Lys Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp 545 550 555 560 Leu Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro 565 570 575 Asn Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys 580 585 590 Ala Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr 595 600 605 Asn Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu 610 615 620 Thr Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser 625 630 635 640 His Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu 645 650 655 Leu Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile 660 665 670 Asn His Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala 675 680 685 Val Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg 690 695 700 Ser Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val 705 710 715 720 Lys Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg 725 730 735 Arg His Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu 740 745 750 Ser Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu 755 760 765 Asn Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly 770 775 780 Ile Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys 785 790 795 800 Glu Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp 805 810 815 Thr Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu 820 825 830 Glu Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr 835 840 845 His Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn 850 855 860 Arg Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala 865 870 875 880 Phe Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg 885 890 895 Glu Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile 900 905 910 Lys Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys 915 920 925 Asn Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro 930 935 940 Arg Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe 945 950 955 960 Arg Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His 965 970 975 His Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val 980 985 990 Thr Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val 995 1000 1005 Lys Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu 1010 1015 1020 Leu Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser 1025 1030 1035 Glu Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val 1040 1045 1050 Ser Arg Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln 1055 1060 1065 Thr Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile 1070 1075 1080 Ile Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn 1085 1090 1095 Gly Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr 1100 1105 1110 Glu Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys 1115 1120 1125 Lys Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr 1130 1135 1140 Gly Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser 1145 1150 1155 Phe Val Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu 1160 1165 1170 Val Arg Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val 1175 1180 1185 Pro Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys 1190 1195 1200 Val Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp 1205 1210 1215 Asn Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val 1220 1225 1230 Arg Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr 1235 1240 1245 Leu Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys 1250 1255 1260 Pro Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu 1265 1270 1275 Asp Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu 1280 1285 1290 Val Arg Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys 1295 1300 1305 Arg Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 528 <211> 1322 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50180-nAPG07433.1 protein sequence" <400> 528 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asn Pro Glu His Asp His Glu Tyr Trp Met Arg His Ala Leu Asn 35 40 45 Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Thr Leu Val Tyr Gly Val Arg Asn Glu Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Met Asn Val Leu Gly Tyr Pro Gly Met Asn His Gln 145 150 155 160 Val Asn Val Ile Gly Gly Val Leu Ala Gln Asp Cys Ser Ala Arg Leu 165 170 175 Cys Asp Phe Tyr Arg Met Pro Arg Gln Gln Lys Asn Gln Gln Arg Ala 180 185 190 Glu Leu Lys Ala Gln Gly Asp Ser Gly Gly Ser Ser Gly Gly Ser Ser 195 200 205 Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser 210 215 220 Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly 225 230 235 240 Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser 245 250 255 Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln 260 265 270 Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser 275 280 285 Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn 290 295 300 Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His 305 310 315 320 Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys 325 330 335 Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu 340 345 350 Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg 355 360 365 Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr 370 375 380 Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu 385 390 395 400 Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys 405 410 415 Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser 420 425 430 Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg 435 440 445 Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu 450 455 460 Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu 465 470 475 480 Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile 485 490 495 Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val 500 505 510 Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln 515 520 525 Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys 530 535 540 Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu 545 550 555 560 Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn 565 570 575 Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala 580 585 590 Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn 595 600 605 Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr 610 615 620 Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His 625 630 635 640 Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu 645 650 655 Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn 660 665 670 His Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val 675 680 685 Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser 690 695 700 Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys 705 710 715 720 Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg 725 730 735 His Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser 740 745 750 Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn 755 760 765 Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile 770 775 780 Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu 785 790 795 800 Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr 805 810 815 Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu 820 825 830 Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His 835 840 845 Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg 850 855 860 Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe 865 870 875 880 Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu 885 890 895 Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys 900 905 910 Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn 915 920 925 Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg 930 935 940 Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg 945 950 955 960 Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His 965 970 975 Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val Thr 980 985 990 Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys 995 1000 1005 Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu 1010 1015 1020 Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu 1025 1030 1035 Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser 1040 1045 1050 Arg Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr 1055 1060 1065 Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile 1070 1075 1080 Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly 1085 1090 1095 Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu 1100 1105 1110 Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys 1115 1120 1125 Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly 1130 1135 1140 Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe 1145 1150 1155 Val Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val 1160 1165 1170 Arg Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro 1175 1180 1185 Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val 1190 1195 1200 Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn 1205 1210 1215 Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg 1220 1225 1230 Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu 1235 1240 1245 Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro 1250 1255 1260 Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp 1265 1270 1275 Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val 1280 1285 1290 Arg Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg 1295 1300 1305 Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 529 <211> 1322 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50181-nAPG07433.1 protein sequence" <400> 529 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asp Pro Glu Leu Asn His Glu Tyr Trp Met Arg His Ala Leu Gln 35 40 45 Leu Ala Gln Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Leu Asn Asn Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Leu Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ser Gly Ala Met Ile His Ser 115 120 125 Arg Ile Gly Thr Val Val Tyr Gly Val Arg Asn Glu Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Leu Asn Val Leu Ser Tyr Pro Gly Met Asn His Gln 145 150 155 160 Val Lys Val Ile Gly Glu Val Leu Ala Pro Ala Cys Ser Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg Met Pro Arg Gln Gln Lys Asn Gln Gln Lys Ala 180 185 190 Glu Trp Lys Leu Ser Gly Glu Ser Gly Gly Ser Ser Gly Gly Ser Ser 195 200 205 Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Ser 210 215 220 Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr Arg Ile Gly 225 230 235 240 Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile Glu Leu Ser 245 250 255 Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile Val Asp Gln 260 265 270 Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr Gly Ala Ser 275 280 285 Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg Arg Leu Asn 290 295 300 Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu Val Gln His 305 310 315 320 Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro Leu Ser Lys 325 330 335 Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu Asp Arg Leu 340 345 350 Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu Ala Gln Arg 355 360 365 Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp Thr Glu Thr 370 375 380 Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg Leu Ser Leu 385 390 395 400 Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp Phe Ser Lys 405 410 415 Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe Ser Val Ser 420 425 430 Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala Ala Gln Arg 435 440 445 Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu Thr Tyr Leu 450 455 460 Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn Ala Ile Leu 465 470 475 480 Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu Arg Arg Ile 485 490 495 Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu Asp Gln Val 500 505 510 Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr Lys Glu Gln 515 520 525 Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp Tyr Tyr Lys 530 535 540 Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg Lys Trp Leu 545 550 555 560 Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr Asp Pro Asn 565 570 575 Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn Leu Lys Ala 580 585 590 Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu Arg Thr Asn 595 600 605 Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr Ala Leu Thr 610 615 620 Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys Ser Ser His 625 630 635 640 Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu Glu Leu Leu 645 650 655 Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys Ala Ile Asn 660 665 670 His Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys Glu Ala Val 675 680 685 Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu Lys Arg Ser 690 695 700 Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro Ile Val Lys 705 710 715 720 Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile Ile Arg Arg 725 730 735 His Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg Glu Leu Ser 740 745 750 Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln Asp Glu Asn 755 760 765 Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu His Gly Ile 770 775 780 Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu Trp Lys Glu 785 790 795 800 Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro Ala Asp Thr 805 810 815 Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro Ile Leu Glu 820 825 830 Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp Ser Tyr His 835 840 845 Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys Gly Asn Arg 850 855 860 Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp Glu Ala Phe 865 870 875 880 Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys Lys Arg Glu 885 890 895 Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu Leu Ile Lys 900 905 910 Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe Leu Lys Asn 915 920 925 Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp Asn Pro Arg 930 935 940 Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala His Phe Arg 945 950 955 960 Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr Leu His His 965 970 975 Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His Met Val Thr 980 985 990 Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys Ser Val Lys 995 1000 1005 Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg Asp Glu Leu 1010 1015 1020 Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys Ile Ser Glu 1025 1030 1035 Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile Phe Val Ser 1040 1045 1050 Arg Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His Lys Gln Thr 1055 1060 1065 Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys Thr Ile Ile 1070 1075 1080 Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp Glu Asn Gly 1085 1090 1095 Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala Thr Tyr Glu 1100 1105 1110 Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn Ser Lys Lys 1115 1120 1125 Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys Gly Thr Gly 1130 1135 1140 Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala Lys Ser Phe 1145 1150 1155 Val Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly Asp Leu Val 1160 1165 1170 Arg Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr Met Val Pro 1175 1180 1185 Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro Lys Lys Val 1190 1195 1200 Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr Leu Asp Asn 1205 1210 1215 Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp Leu Val Arg 1220 1225 1230 Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe Gly Thr Leu 1235 1240 1245 Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val Asn Lys Pro 1250 1255 1260 Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr Ile Glu Asp 1265 1270 1275 Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu Arg Leu Val 1280 1285 1290 Arg Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly Ser Lys Arg 1295 1300 1305 Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 1310 1315 1320 <210> 530 <211> 1325 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="LPG50182-nAPG07433.1 protein sequence" <400> 530 Met Ala Pro Lys Lys Lys Arg Lys Val Asp Tyr Lys Asp His Asp Gly 1 5 10 15 Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Met 20 25 30 Ser Asn Pro Glu Leu Asn His Glu Tyr Trp Met Arg Tyr Ala Leu Thr 35 40 45 Leu Ala Lys Arg Ala Arg Asp Glu Gly Glu Val Pro Val Gly Ala Val 50 55 60 Leu Val Tyr His Asp Gln Val Ile Gly Glu Gly Trp Asn Arg Ala Ile 65 70 75 80 Gly Leu His Asp Pro Thr Ala His Ala Glu Ile Met Ala Leu Arg Gln 85 90 95 Gly Gly Leu Val Leu Gln Asn Tyr Arg Leu Ile Asp Thr Thr Leu Tyr 100 105 110 Val Thr Phe Glu Pro Cys Val Met Cys Ala Gly Ala Met Val His Ser 115 120 125 Arg Ile Gly Arg Leu Val Phe Gly Val Arg Asn Ser Lys Arg Gly Ala 130 135 140 Ala Gly Ser Leu Leu Asn Val Leu Asn Tyr Pro Gly Met Asn His Gln 145 150 155 160 Ile Asp Met Glu Gly Val Leu Arg Asp Glu Cys Ala Ala Met Leu 165 170 175 Cys Asp Phe Tyr Arg Leu Pro Arg Ile Val Lys Asn Ala Leu Lys Gln 180 185 190 Ser Pro Pro Asp Ser Thr Asn Leu His Ala Ser Gly Gly Ser Ser Gly 195 200 205 Gly Ser Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro 210 215 220 Glu Ser Ser Gly Gly Ser Ser Gly Gly Ser Met Arg Glu Leu Asp Tyr 225 230 235 240 Arg Ile Gly Leu Ala Ile Gly Thr Asn Ser Ile Gly Trp Gly Val Ile 245 250 255 Glu Leu Ser Trp Asn Lys Asp Arg Glu Arg Tyr Glu Lys Val Arg Ile 260 265 270 Val Asp Gln Gly Val Arg Met Phe Asp Arg Ala Glu Met Pro Lys Thr 275 280 285 Gly Ala Ser Leu Ala Glu Pro Arg Arg Ile Ala Arg Ser Ser Arg Arg 290 295 300 Arg Leu Asn Arg Lys Ser Gln Arg Lys Lys Asn Ile Arg Asn Leu Leu 305 310 315 320 Val Gln His Gly Val Ile Thr Gln Glu Glu Leu Asp Ser Leu Tyr Pro 325 330 335 Leu Ser Lys Lys Ser Met Asp Ile Trp Gly Ile Arg Leu Asp Gly Leu 340 345 350 Asp Arg Leu Leu Asn His Phe Glu Trp Ala Arg Leu Leu Ile His Leu 355 360 365 Ala Gln Arg Arg Gly Phe Lys Ser Asn Arg Lys Ser Glu Leu Lys Asp 370 375 380 Thr Glu Thr Gly Lys Val Leu Ser Ser Ile Gln Leu Asn Glu Lys Arg 385 390 395 400 Leu Ser Leu Tyr Arg Thr Val Gly Glu Met Trp Met Lys Asp Pro Asp 405 410 415 Phe Ser Lys Tyr Asp Arg Lys Arg Asn Ser Pro Asn Glu Tyr Val Phe 420 425 430 Ser Val Ser Arg Ala Glu Leu Glu Lys Glu Ile Val Thr Leu Phe Ala 435 440 445 Ala Gln Arg Arg Phe Gln Ser Pro Tyr Ala Ser Lys Asp Leu Gln Glu 450 455 460 Thr Tyr Leu Gln Ile Trp Thr His Gln Leu Pro Phe Ala Ser Gly Asn 465 470 475 480 Ala Ile Leu Asn Lys Val Gly Tyr Cys Ser Leu Leu Lys Gly Lys Glu 485 490 495 Arg Arg Ile Pro Lys Ala Thr Tyr Thr Phe Gln Tyr Phe Ser Ala Leu 500 505 510 Asp Gln Val Asn Arg Thr Arg Leu Gly Pro Asp Phe Gln Pro Phe Thr 515 520 525 Lys Glu Gln Arg Glu Ile Ile Leu Asn Asn Met Phe Gln Arg Thr Asp 530 535 540 Tyr Tyr Lys Lys Lys Thr Ile Pro Glu Val Thr Tyr Tyr Asp Ile Arg 545 550 555 560 Lys Trp Leu Glu Leu Asp Glu Thr Ile Gln Phe Lys Gly Leu Asn Tyr 565 570 575 Asp Pro Asn Glu Glu Leu Lys Lys Ile Glu Lys Lys Pro Phe Ile Asn 580 585 590 Leu Lys Ala Phe Tyr Glu Ile Asn Lys Val Val Ala Asn Tyr Ser Glu 595 600 605 Arg Thr Asn Glu Thr Phe Ser Thr Leu Asp Tyr Asp Gly Ile Gly Tyr 610 615 620 Ala Leu Thr Val Tyr Lys Thr Asp Lys Asp Ile Arg Ser Tyr Leu Lys 625 630 635 640 Ser Ser His Asn Leu Pro Lys Arg Cys Tyr Asp Asp Gln Leu Ile Glu 645 650 655 Glu Leu Leu Ser Leu Ser Tyr Thr Lys Phe Gly His Leu Ser Leu Lys 660 665 670 Ala Ile Asn His Val Leu Ser Ile Met Gln Lys Gly Asn Thr Tyr Lys 675 680 685 Glu Ala Val Asp Gln Leu Gly Tyr Asp Thr Ser Gly Leu Lys Lys Glu 690 695 700 Lys Arg Ser Lys Phe Leu Pro Pro Ile Ser Asp Glu Ile Thr Asn Pro 705 710 715 720 Ile Val Lys Arg Ala Leu Thr Gln Ala Arg Lys Val Val Asn Ala Ile 725 730 735 Ile Arg Arg His Gly Ser Pro His Ser Val His Ile Glu Leu Ala Arg 740 745 750 Glu Leu Ser Lys Asn His Asp Glu Arg Thr Lys Ile Val Ser Ala Gln 755 760 765 Asp Glu Asn Tyr Lys Lys Asn Lys Gly Ala Ile Ser Ile Leu Ser Glu 770 775 780 His Gly Ile Leu Asn Pro Thr Gly Tyr Asp Ile Val Arg Tyr Lys Leu 785 790 795 800 Trp Lys Glu Gln Gly Glu Arg Cys Ala Tyr Ser Leu Lys Glu Ile Pro 805 810 815 Ala Asp Thr Phe Phe Asn Glu Leu Lys Lys Glu Arg Asn Gly Ala Pro 820 825 830 Ile Leu Glu Val Asp His Ile Leu Pro Tyr Ser Gln Ser Phe Ile Asp 835 840 845 Ser Tyr His Asn Lys Val Leu Val Tyr Ser Asp Glu Asn Arg Lys Lys 850 855 860 Gly Asn Arg Ile Pro Tyr Thr Tyr Phe Leu Glu Thr Asn Lys Asp Trp 865 870 875 880 Glu Ala Phe Glu Arg Tyr Val Arg Ser Asn Lys Phe Phe Ser Lys Lys 885 890 895 Lys Arg Glu Tyr Leu Leu Lys Arg Ala Tyr Leu Pro Arg Glu Ser Glu 900 905 910 Leu Ile Lys Glu Arg His Leu Asn Asp Thr Arg Tyr Ala Ser Thr Phe 915 920 925 Leu Lys Asn Phe Ile Glu Gln Asn Leu Gln Phe Lys Glu Ala Glu Asp 930 935 940 Asn Pro Arg Lys Arg Arg Val Gln Thr Val Asn Gly Val Ile Thr Ala 945 950 955 960 His Phe Arg Lys Arg Trp Gly Leu Glu Lys Asp Arg Gln Glu Thr Tyr 965 970 975 Leu His His Ala Met Asp Ala Ile Ile Val Ala Cys Thr Asp His His 980 985 990 Met Val Thr Arg Val Thr Glu Tyr Tyr Gln Ile Lys Glu Ser Asn Lys 995 1000 1005 Ser Val Lys Lys Pro Tyr Phe Pro Met Pro Trp Glu Gly Phe Arg 1010 1015 1020 Asp Glu Leu Leu Ser His Leu Ala Ser Gln Pro Ile Ala Lys Lys 1025 1030 1035 Ile Ser Glu Glu Leu Lys Ala Gly Tyr Gln Ser Leu Asp Tyr Ile 1040 1045 1050 Phe Val Ser Arg Met Pro Lys Arg Ser Ile Thr Gly Ala Ala His 1055 1060 1065 Lys Gln Thr Ile Met Arg Lys Gly Gly Ile Asp Lys Lys Gly Lys 1070 1075 1080 Thr Ile Ile Ile Glu Arg Leu His Leu Lys Asp Ile Lys Phe Asp 1085 1090 1095 Glu Asn Gly Asp Phe Lys Met Val Gly Lys Glu Gln Asp Met Ala 1100 1105 1110 Thr Tyr Glu Ala Ile Lys Gln Arg Tyr Leu Glu His Gly Lys Asn 1115 1120 1125 Ser Lys Lys Ala Phe Glu Thr Pro Leu Tyr Lys Pro Ser Lys Lys 1130 1135 1140 Gly Thr Gly Asn Leu Ile Lys Arg Val Lys Val Glu Gly Gln Ala 1145 1150 1155 Lys Ser Phe Val Arg Glu Val Asn Gly Gly Val Ala Gln Asn Gly 1160 1165 1170 Asp Leu Val Arg Val Asp Leu Phe Glu Lys Asp Asp Lys Tyr Tyr 1175 1180 1185 Met Val Pro Ile Tyr Val Pro Asp Thr Val Cys Ser Glu Leu Pro 1190 1195 1200 Lys Lys Val Val Ala Ser Ser Lys Gly Tyr Glu Gln Trp Leu Thr 1205 1210 1215 Leu Asp Asn Ser Phe Thr Phe Lys Phe Ser Leu Tyr Pro Tyr Asp 1220 1225 1230 Leu Val Arg Leu Val Lys Gly Asp Glu Asp Arg Phe Leu Tyr Phe 1235 1240 1245 Gly Thr Leu Asp Ile Asp Ser Asp Arg Leu Asn Phe Lys Asp Val 1250 1255 1260 Asn Lys Pro Ser Lys Lys Asn Glu Tyr Arg Tyr Ser Leu Lys Thr 1265 1270 1275 Ile Glu Asp Leu Glu Lys Tyr Glu Val Gly Val Leu Gly Asp Leu 1280 1285 1290 Arg Leu Val Arg Lys Glu Thr Arg Arg Asn Phe His Ser Gly Gly 1295 1300 1305 Ser Lys Arg Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys 1310 1315 1320 Lys Lys 1325 <210> 531 <211> 130 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000139" <400> 531 agguuuuaau ggcccagccu gucauaguuc cauuaaagcc aaaaguggcu uugauguuuc 60 uaugauaagg guuucgaccc guggcgucgg ggaucgccug cccauugaaa ugggcuucuc 120 cccauuuauu 130 <210> 532 <211> 130 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000143" <400> 532 cauggcagua cauuagagca gucauaguuc cauuaaagcc aaaaguggcu uugauguuuc 60 uaugauaagg guuucgaccc guggcgucgg ggaucgccug cccauugaaa ugggcuucuc 120 cccauuuauu 130 <210> 533 <211> 130 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000186" <400> 533 ggacagugcg caucucccug gucauaguuc cauuaaagcc aaaaguggcu uugauguuuc 60 uaugauaagg guuucgaccc guggcgucgg ggaucgccug cccauugaaa ugggcuucuc 120 cccauuuauu 130 <210> 534 <211> 130 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000194" <400> 534 gccgcacagc auucaggucg gucauaguuc cauuaaagcc aaaaguggcu uugauguuuc 60 uaugauaagg guuucgaccc guggcgucgg ggaucgccug cccauugaaa ugggcuucuc 120 cccauuuauu 130 <210> 535 <211> 135 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN000930" <400> 535 gaacaacuca aauggaaaug aauaugucau aguuccauga aagccaaaag uggcuuugau 60 guuucuauga uaaggguuuc ggcccguggc gucggggauc gccugcccau uccgaugggc 120 uucuccccau uuauu 135 <210> 536 <211> 130 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN001681" <400> 536 ccgugccuug accuacccug gucauaguuc cauuaaagcc aaaaguggcu uugauguuuc 60 uaugauaagg guuucgaccc guggcgucgg ggaucgccug cccauugaaa ugggcuucuc 120 cccauuuauu 130 <210> 537 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000139 target sequence" <400> 537 aggttttaat ggcccagcct 20 <210> 538 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000143 target sequence" <400> 538 catggcagta cattagagca 20 <210> 539 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000186 target sequence" <400> 539 ggacagtgcg catctccctg 20 <210> 540 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000194 target sequence" <400> 540 gccgcacagc attcaggtcg 20 <210> 541 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000930 target sequence" <400> 541 gaacaactca aatggaaatg aatat 25 <210> 542 <211> 20 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN001681 target sequence" <400> 542 ccgtgccttg acctaccctg 20 <210> 543 <211> 53 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000139 forward primer" <400> 543 tcgtcggcag cgtcagatgt gtataagaga cagcttgtag ctggaggtcc atc 53 <210> 544 <211> 52 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000143 forward primer" <400> 544 tcgtcggcag cgtcagatgt gtataagaga cagacatttg acgagcagcg aa 52 <210> 545 <211> 53 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000186 forward primer" <400> 545 tcgtcggcag cgtcagatgt gtataagaga cagtggcccc tatgtggaga tca 53 <210> 546 <211> 53 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000194 forward primer" <400> 546 tcgtcggcag cgtcagatgt gttaagaga cagatgacat tcaggccaca gtg 53 <210> 547 <211> 53 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000930 forward primer" <400> 547 tcgtcggcag cgtcagatgt gtataagaga caggacagcc aagaggtttt gcc 53 <210> 548 <211> 53 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN001681 forward primer" <400> 548 tcgtcggcag cgtcagatgt gtataagaga cagtggtgga actggacggg gat 53 <210> 549 <211> 54 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000139 reverse primer" <400> 549 gtctcgtggg ctcggagatg tgtataagag acagtgttgg caaatctagt ctcg 54 <210> 550 <211> 54 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000143 reverse primer" <400> 550 gtctcgtggg ctcggagatg tgtataagag acagggcccc tggagaggtt ttaa 54 <210> 551 <211> 54 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000186 reverse primer" <400> 551 gtctcgtggg ctcggagatg tgtataagag acagggcaga gctcagcctc atag 54 <210> 552 <211> 54 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000194 reverse primer" <400> 552 gtctcgtggg ctcggagatg tgtataagag acagcttcct cctattcagg ccca 54 <210> 553 <211> 54 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN000930 reverse primer" <400> 553 gtctcgtggg ctcggagatg tgtataagag acagctgtcc cttgcagctt ctgt 54 <210> 554 <211> 54 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN001681 reverse primer" <400> 554 gtctcgtggg ctcggagatg tgtataagag acagcagctt gtggcccagg atgt 54 <210> 555 <211> 1368 <212> PRT <213> Streptococcus pyogenes <220> <221> source <223> /note="Streptococcus pyogenes Cas9" <400> 555 Met Asp Lys Lys Tyr Ser Ile Gly Leu Asp Ile Gly Thr Asn Ser Val 1 5 10 15 Gly Trp Ala Val Ile Thr Asp Asp Tyr Lys Val Pro Ser Lys Lys Leu 20 25 30 Lys Gly Leu Gly Asn Thr Asp Arg His Gly Ile Lys Lys Asn Leu Ile 35 40 45 Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr Ala Glu Ala Thr Arg Leu 50 55 60 Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Lys Asn Arg Ile Cys 65 70 75 80 Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met Ala Lys Val Asp Asp Ser 85 90 95 Phe Phe His Arg Leu Glu Glu Ser Phe Leu Val Glu Glu Asp Lys Lys 100 105 110 His Glu Arg His Pro Ile Phe Gly Asn Ile Val Asp Glu Val Ala Tyr 115 120 125 His Glu Lys Tyr Pro Thr Ile Tyr His Leu Arg Lys Lys Leu Ala Asp 130 135 140 Ser Thr Asp Lys Val Asp Leu Arg Leu Ile Tyr Leu Ala Leu Ala His 145 150 155 160 Met Ile Lys Phe Arg Gly His Phe Leu Ile Glu Gly Asp Leu Asn Pro 165 170 175 Asp Asn Ser Asp Val Asp Lys Leu Phe Ile Gln Leu Val Gln Thr Tyr 180 185 190 Asn Gln Leu Phe Glu Asn Pro Ile Asn Ala Ser Arg Val Asp Ala 195 200 205 Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys Ser Arg Arg Leu Glu Asn 210 215 220 Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys Asn Gly Leu Phe Gly Asn 225 230 235 240 Leu Ile Ala Leu Ser Leu Gly Leu Thr Pro Asn Phe Lys Ser Asn Phe 245 250 255 Asp Leu Ala Glu Asp Ala Lys Leu Gln Leu Ser Lys Asp Thr Tyr Asp 260 265 270 Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile Gly Asp Gln Tyr Ala Asp 275 280 285 Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp Ala Thr Leu Leu Ser Asp 290 295 300 Ile Leu Arg Val Asn Ser Glu Ile Thr Lys Ala Pro Leu Ser Ala Ser 305 310 315 320 Met Ile Lys Arg Tyr Asp Glu His His Gln Asp Leu Thr Leu Leu Lys 325 330 335 Ala Leu Val Arg Gln Gln Leu Pro Glu Lys Tyr Lys Glu Ile Phe Phe 340 345 350 Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Gly Ala Ser 355 360 365 Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro Ile Leu Glu Lys Met Asp 370 375 380 Gly Thr Glu Glu Leu Leu Ala Lys Leu Asn Arg Glu Asp Leu Leu Arg 385 390 395 400 Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro Tyr Gln Ile His Leu 405 410 415 Gly Glu Leu His Ala Ile Leu Arg Arg Gln Glu Asp Phe Tyr Pro Phe 420 425 430 Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys Ile Leu Thr Phe Arg Ile 435 440 445 Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser Arg Phe Ala Trp 450 455 460 Met Thr Arg Lys Ser Glu Glu Thr Ile Thr Pro Trp Asn Phe Glu Glu 465 470 475 480 Val Val Asp Lys Gly Ala Ser Ala Gln Ser Phe Ile Glu Arg Met Thr 485 490 495 Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys Val Leu Pro Lys His Ser 500 505 510 Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn Glu Leu Thr Lys Val Lys 515 520 525 Tyr Val Thr Glu Gly Met Arg Lys Pro Ala Phe Leu Ser Gly Glu Gln 530 535 540 Lys Lys Ala Ile Val Asp Leu Leu Phe Lys Thr Asn Arg Lys Val Thr 545 550 555 560 Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys Lys Ile Glu Cys Phe Asp 565 570 575 Ser Val Glu Ile Ser Gly Val Glu Asp Arg Phe Asn Ala Ser Leu Gly 580 585 590 Thr Tyr His Asp Leu Leu Lys Ile Ile Lys Asp Lys Asp Phe Leu Asp 595 600 605 Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp Ile Val Leu Thr Leu Thr 610 615 620 Leu Phe Glu Asp Arg Glu Met Ile Glu Glu Arg Leu Lys Thr Tyr Ala 625 630 635 640 His Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys Arg Arg Arg Tyr 645 650 655 Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn Gly Ile Arg Asp 660 665 670 Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys Ser Asp Gly Phe 675 680 685 Ala Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ser Leu Thr Phe 690 695 700 Lys Glu Asp Ile Gln Lys Ala Gln Val Ser Gly Gln Gly Asp Ser Leu 705 710 715 720 His Glu His Ile Ala Asn Leu Ala Gly Ser Pro Ala Ile Lys Lys Gly 725 730 735 Ile Leu Gln Thr Val Lys Val Val Asp Glu Leu Val Lys Val Met Gly 740 745 750 Arg His Lys Pro Glu Asn Ile Val Ile Glu Met Ala Arg Glu Asn Gln 755 760 765 Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg Glu Arg Met Lys Arg Ile 770 775 780 Glu Glu Gly Ile Lys Glu Leu Gly Ser Asp Ile Leu Lys Glu Tyr Pro 785 790 795 800 Val Glu Asn Thr Gln Leu Gln Asn Glu Lys Leu Tyr Leu Tyr Tyr Leu 805 810 815 Gln Asn Gly Arg Asp Met Tyr Val Asp Gln Glu Leu Asp Ile Asn Arg 820 825 830 Leu Ser Asp Tyr Asp Val Asp His Ile Val Pro Gln Ser Phe Leu Lys 835 840 845 Asp Asp Ser Ile Asp Asn Lys Val Leu Thr Arg Ser Asp Lys Asn Arg 850 855 860 Gly Lys Ser Asp Asn Val Pro Ser Glu Glu Val Val Lys Lys Met Lys 865 870 875 880 Asn Tyr Trp Arg Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys 885 890 895 Phe Asp Asn Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp 900 905 910 Lys Val Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr 915 920 925 Lys His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp 930 935 940 Glu Asn Asp Lys Leu Ile Arg Glu Val Arg Val Ile Thr Leu Lys Ser 945 950 955 960 Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys Val Arg 965 970 975 Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu Asn Ala Val 980 985 990 Val Gly Thr Ala Leu Ile Lys Lys Tyr Pro Lys Leu Glu Ser Glu Phe 995 1000 1005 Val Tyr Gly Asp Tyr Lys Val Tyr Asp Val Arg Lys Met Ile Ala 1010 1015 1020 Lys Ser Glu Gln Glu Ile Gly Lys Ala Thr Ala Lys Tyr Phe Phe 1025 1030 1035 Tyr Ser Asn Ile Met Asn Phe Phe Lys Thr Glu Ile Thr Leu Ala 1040 1045 1050 Asn Gly Glu Ile Arg Lys Arg Pro Leu Ile Glu Thr Asn Gly Glu 1055 1060 1065 Thr Gly Glu Ile Val Trp Asp Lys Gly Arg Asp Phe Ala Thr Val 1070 1075 1080 Arg Lys Val Leu Ser Met Pro Gln Val Asn Ile Val Lys Lys Thr 1085 1090 1095 Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro Lys 1100 1105 1110 Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 1115 1120 1125 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val 1130 1135 1140 Leu Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys 1145 1150 1155 Ser Val Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser 1160 1165 1170 Phe Glu Lys Asp Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys 1175 1180 1185 Glu Val Arg Lys Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu 1190 1195 1200 Phe Glu Leu Glu Asn Gly Arg Lys Arg Met Leu Ala Ser Ala Gly 1205 1210 1215 Glu Leu Gln Lys Gly Asn Glu Leu Ala Leu Pro Ser Lys Tyr Val 1220 1225 1230 Asn Phe Leu Tyr Leu Ala Ser His Tyr Glu Lys Leu Lys Gly Ser 1235 1240 1245 Pro Glu Asp Asn Glu Gln Lys Gln Leu Phe Val Glu Gln His Lys 1250 1255 1260 His Tyr Leu Asp Glu Ile Ile Glu Gln Ile Ser Glu Phe Ser Lys 1265 1270 1275 Arg Val Ile Leu Ala Asp Ala Asn Leu Asp Lys Val Leu Ser Ala 1280 1285 1290 Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu Gln Ala Glu Asn 1295 1300 1305 Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala Pro Ala Ala 1310 1315 1320 Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Arg Tyr Thr Ser 1325 1330 1335 Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile Thr 1340 1345 1350 Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 1355 1360 1365 <210> 556 <211> 1368 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="Streptococcus pyogenes Cas9 D10A nickase" <400> 556 Met Asp Lys Lys Tyr Ser Ile Gly Leu Ala Ile Gly Thr Asn Ser Val 1 5 10 15 Gly Trp Ala Val Ile Thr Asp Asp Tyr Lys Val Pro Ser Lys Lys Leu 20 25 30 Lys Gly Leu Gly Asn Thr Asp Arg His Gly Ile Lys Lys Asn Leu Ile 35 40 45 Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr Ala Glu Ala Thr Arg Leu 50 55 60 Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Lys Asn Arg Ile Cys 65 70 75 80 Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met Ala Lys Val Asp Asp Ser 85 90 95 Phe Phe His Arg Leu Glu Glu Ser Phe Leu Val Glu Glu Asp Lys Lys 100 105 110 His Glu Arg His Pro Ile Phe Gly Asn Ile Val Asp Glu Val Ala Tyr 115 120 125 His Glu Lys Tyr Pro Thr Ile Tyr His Leu Arg Lys Lys Leu Ala Asp 130 135 140 Ser Thr Asp Lys Val Asp Leu Arg Leu Ile Tyr Leu Ala Leu Ala His 145 150 155 160 Met Ile Lys Phe Arg Gly His Phe Leu Ile Glu Gly Asp Leu Asn Pro 165 170 175 Asp Asn Ser Asp Val Asp Lys Leu Phe Ile Gln Leu Val Gln Thr Tyr 180 185 190 Asn Gln Leu Phe Glu Asn Pro Ile Asn Ala Ser Arg Val Asp Ala 195 200 205 Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys Ser Arg Arg Leu Glu Asn 210 215 220 Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys Asn Gly Leu Phe Gly Asn 225 230 235 240 Leu Ile Ala Leu Ser Leu Gly Leu Thr Pro Asn Phe Lys Ser Asn Phe 245 250 255 Asp Leu Ala Glu Asp Ala Lys Leu Gln Leu Ser Lys Asp Thr Tyr Asp 260 265 270 Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile Gly Asp Gln Tyr Ala Asp 275 280 285 Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp Ala Thr Leu Leu Ser Asp 290 295 300 Ile Leu Arg Val Asn Ser Glu Ile Thr Lys Ala Pro Leu Ser Ala Ser 305 310 315 320 Met Ile Lys Arg Tyr Asp Glu His His Gln Asp Leu Thr Leu Leu Lys 325 330 335 Ala Leu Val Arg Gln Gln Leu Pro Glu Lys Tyr Lys Glu Ile Phe Phe 340 345 350 Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Gly Ala Ser 355 360 365 Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro Ile Leu Glu Lys Met Asp 370 375 380 Gly Thr Glu Glu Leu Leu Ala Lys Leu Asn Arg Glu Asp Leu Leu Arg 385 390 395 400 Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro Tyr Gln Ile His Leu 405 410 415 Gly Glu Leu His Ala Ile Leu Arg Arg Gln Glu Asp Phe Tyr Pro Phe 420 425 430 Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys Ile Leu Thr Phe Arg Ile 435 440 445 Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser Arg Phe Ala Trp 450 455 460 Met Thr Arg Lys Ser Glu Glu Thr Ile Thr Pro Trp Asn Phe Glu Glu 465 470 475 480 Val Val Asp Lys Gly Ala Ser Ala Gln Ser Phe Ile Glu Arg Met Thr 485 490 495 Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys Val Leu Pro Lys His Ser 500 505 510 Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn Glu Leu Thr Lys Val Lys 515 520 525 Tyr Val Thr Glu Gly Met Arg Lys Pro Ala Phe Leu Ser Gly Glu Gln 530 535 540 Lys Lys Ala Ile Val Asp Leu Leu Phe Lys Thr Asn Arg Lys Val Thr 545 550 555 560 Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys Lys Ile Glu Cys Phe Asp 565 570 575 Ser Val Glu Ile Ser Gly Val Glu Asp Arg Phe Asn Ala Ser Leu Gly 580 585 590 Thr Tyr His Asp Leu Leu Lys Ile Ile Lys Asp Lys Asp Phe Leu Asp 595 600 605 Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp Ile Val Leu Thr Leu Thr 610 615 620 Leu Phe Glu Asp Arg Glu Met Ile Glu Glu Arg Leu Lys Thr Tyr Ala 625 630 635 640 His Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys Arg Arg Arg Tyr 645 650 655 Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn Gly Ile Arg Asp 660 665 670 Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys Ser Asp Gly Phe 675 680 685 Ala Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ser Leu Thr Phe 690 695 700 Lys Glu Asp Ile Gln Lys Ala Gln Val Ser Gly Gln Gly Asp Ser Leu 705 710 715 720 His Glu His Ile Ala Asn Leu Ala Gly Ser Pro Ala Ile Lys Lys Gly 725 730 735 Ile Leu Gln Thr Val Lys Val Val Asp Glu Leu Val Lys Val Met Gly 740 745 750 Arg His Lys Pro Glu Asn Ile Val Ile Glu Met Ala Arg Glu Asn Gln 755 760 765 Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg Glu Arg Met Lys Arg Ile 770 775 780 Glu Glu Gly Ile Lys Glu Leu Gly Ser Asp Ile Leu Lys Glu Tyr Pro 785 790 795 800 Val Glu Asn Thr Gln Leu Gln Asn Glu Lys Leu Tyr Leu Tyr Tyr Leu 805 810 815 Gln Asn Gly Arg Asp Met Tyr Val Asp Gln Glu Leu Asp Ile Asn Arg 820 825 830 Leu Ser Asp Tyr Asp Val Asp His Ile Val Pro Gln Ser Phe Leu Lys 835 840 845 Asp Asp Ser Ile Asp Asn Lys Val Leu Thr Arg Ser Asp Lys Asn Arg 850 855 860 Gly Lys Ser Asp Asn Val Pro Ser Glu Glu Val Val Lys Lys Met Lys 865 870 875 880 Asn Tyr Trp Arg Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys 885 890 895 Phe Asp Asn Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp 900 905 910 Lys Val Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr 915 920 925 Lys His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp 930 935 940 Glu Asn Asp Lys Leu Ile Arg Glu Val Arg Val Ile Thr Leu Lys Ser 945 950 955 960 Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys Val Arg 965 970 975 Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu Asn Ala Val 980 985 990 Val Gly Thr Ala Leu Ile Lys Lys Tyr Pro Lys Leu Glu Ser Glu Phe 995 1000 1005 Val Tyr Gly Asp Tyr Lys Val Tyr Asp Val Arg Lys Met Ile Ala 1010 1015 1020 Lys Ser Glu Gln Glu Ile Gly Lys Ala Thr Ala Lys Tyr Phe Phe 1025 1030 1035 Tyr Ser Asn Ile Met Asn Phe Phe Lys Thr Glu Ile Thr Leu Ala 1040 1045 1050 Asn Gly Glu Ile Arg Lys Arg Pro Leu Ile Glu Thr Asn Gly Glu 1055 1060 1065 Thr Gly Glu Ile Val Trp Asp Lys Gly Arg Asp Phe Ala Thr Val 1070 1075 1080 Arg Lys Val Leu Ser Met Pro Gln Val Asn Ile Val Lys Lys Thr 1085 1090 1095 Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro Lys 1100 1105 1110 Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 1115 1120 1125 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val 1130 1135 1140 Leu Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys 1145 1150 1155 Ser Val Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser 1160 1165 1170 Phe Glu Lys Asp Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys 1175 1180 1185 Glu Val Arg Lys Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu 1190 1195 1200 Phe Glu Leu Glu Asn Gly Arg Lys Arg Met Leu Ala Ser Ala Gly 1205 1210 1215 Glu Leu Gln Lys Gly Asn Glu Leu Ala Leu Pro Ser Lys Tyr Val 1220 1225 1230 Asn Phe Leu Tyr Leu Ala Ser His Tyr Glu Lys Leu Lys Gly Ser 1235 1240 1245 Pro Glu Asp Asn Glu Gln Lys Gln Leu Phe Val Glu Gln His Lys 1250 1255 1260 His Tyr Leu Asp Glu Ile Ile Glu Gln Ile Ser Glu Phe Ser Lys 1265 1270 1275 Arg Val Ile Leu Ala Asp Ala Asn Leu Asp Lys Val Leu Ser Ala 1280 1285 1290 Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu Gln Ala Glu Asn 1295 1300 1305 Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala Pro Ala Ala 1310 1315 1320 Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Arg Tyr Thr Ser 1325 1330 1335 Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile Thr 1340 1345 1350 Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 1355 1360 1365 <210> 557 <211> 1388 <212> PRT <213> Streptococcus thermophilus <220> <221> source <223> /note="Streptococcus thermophilus Cas9" <400> 557 Met Thr Lys Pro Tyr Ser Ile Gly Leu Asp Ile Gly Thr Asn Ser Val 1 5 10 15 Gly Trp Ala Val Thr Thr Asp Asn Tyr Lys Val Pro Ser Lys Lys Met 20 25 30 Lys Val Leu Gly Asn Thr Ser Lys Lys Tyr Ile Lys Lys Asn Leu Leu 35 40 45 Gly Val Leu Leu Phe Asp Ser Gly Ile Thr Ala Glu Gly Arg Arg Leu 50 55 60 Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Arg Asn Arg Ile Leu 65 70 75 80 Tyr Leu Gln Glu Ile Phe Ser Thr Glu Met Ala Thr Leu Asp Asp Ala 85 90 95 Phe Phe Gln Arg Leu Asp Asp Ser Phe Leu Val Pro Asp Asp Lys Arg 100 105 110 Asp Ser Lys Tyr Pro Ile Phe Gly Asn Leu Val Glu Glu Lys Ala Tyr 115 120 125 His Asp Glu Phe Pro Thr Ile Tyr His Leu Arg Lys Tyr Leu Ala Asp 130 135 140 Ser Thr Lys Lys Ala Asp Leu Arg Leu Val Tyr Leu Ala Leu Ala His 145 150 155 160 Met Ile Lys Tyr Arg Gly His Phe Leu Ile Glu Gly Glu Phe Asn Ser 165 170 175 Lys Asn Asn Asp Ile Gln Lys Asn Phe Gln Asp Phe Leu Asp Thr Tyr 180 185 190 Asn Ala Ile Phe Glu Ser Asp Leu Ser Leu Glu Asn Ser Lys Gln Leu 195 200 205 Glu Glu Ile Val Lys Asp Lys Ile Ser Lys Leu Glu Lys Lys Asp Arg 210 215 220 Ile Leu Lys Leu Phe Pro Gly Glu Lys Asn Ser Gly Ile Phe Ser Glu 225 230 235 240 Phe Leu Lys Leu Ile Val Gly Asn Gln Ala Asp Phe Arg Lys Cys Phe 245 250 255 Asn Leu Asp Glu Lys Ala Ser Leu His Phe Ser Lys Glu Ser Tyr Asp 260 265 270 Glu Asp Leu Glu Thr Leu Leu Gly Tyr Ile Gly Asp Asp Tyr Ser Asp 275 280 285 Val Phe Leu Lys Ala Lys Lys Leu Tyr Asp Ala Ile Leu Leu Ser Gly 290 295 300 Phe Leu Thr Val Thr Asp Asn Glu Thr Glu Ala Pro Leu Ser Ser Ala 305 310 315 320 Met Ile Lys Arg Tyr Asn Glu His Lys Glu Asp Leu Ala Leu Leu Lys 325 330 335 Glu Tyr Ile Arg Asn Ile Ser Leu Lys Thr Tyr Asn Glu Val Phe Lys 340 345 350 Asp Asp Thr Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Lys Thr Asn 355 360 365 Gln Glu Asp Phe Tyr Val Tyr Leu Lys Lys Leu Leu Ala Glu Phe Glu 370 375 380 Gly Ala Asp Tyr Phe Leu Glu Lys Ile Asp Arg Glu Asp Phe Leu Arg 385 390 395 400 Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro Tyr Gln Ile His Leu 405 410 415 Gln Glu Met Arg Ala Ile Leu Asp Lys Gln Ala Lys Phe Tyr Pro Phe 420 425 430 Leu Ala Lys Asn Lys Glu Arg Ile Glu Lys Ile Leu Thr Phe Arg Ile 435 440 445 Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser Asp Phe Ala Trp 450 455 460 Ser Ile Arg Lys Arg Asn Glu Lys Ile Thr Pro Trp Asn Phe Glu Asp 465 470 475 480 Val Ile Asp Lys Glu Ser Ser Ala Glu Ala Phe Ile Asn Arg Met Thr 485 490 495 Ser Phe Asp Leu Tyr Leu Pro Glu Glu Lys Val Leu Pro Lys His Ser 500 505 510 Leu Leu Tyr Glu Thr Phe Asn Val Tyr Asn Glu Leu Thr Lys Val Arg 515 520 525 Phe Ile Ala Glu Ser Met Arg Asp Tyr Gln Phe Leu Asp Ser Lys Gln 530 535 540 Lys Lys Asp Ile Val Arg Leu Tyr Phe Lys Asp Lys Arg Lys Val Thr 545 550 555 560 Asp Lys Asp Ile Ile Glu Tyr Leu His Ala Ile Tyr Gly Tyr Asp Gly 565 570 575 Ile Glu Leu Lys Gly Ile Glu Lys Gln Phe Asn Ser Ser Leu Ser Thr 580 585 590 Tyr His Asp Leu Leu Asn Ile Ile Asn Asp Lys Glu Phe Leu Asp Asp 595 600 605 Ser Ser Asn Glu Ala Ile Ile Glu Glu Ile Ile His Thr Leu Thr Ile 610 615 620 Phe Glu Asp Arg Glu Met Ile Lys Gln Arg Leu Ser Lys Phe Glu Asn 625 630 635 640 Ile Phe Asp Lys Ser Val Leu Lys Lys Leu Ser Arg Arg His Tyr Thr 645 650 655 Gly Trp Gly Lys Leu Ser Ala Lys Leu Ile Asn Gly Ile Arg Asp Glu 660 665 670 Lys Ser Gly Asn Thr Ile Leu Asp Tyr Leu Ile Asp Asp Gly Ile Ser 675 680 685 Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ala Leu Ser Phe Lys 690 695 700 Lys Lys Ile Gln Lys Ala Gln Ile Ile Gly Asp Glu Asp Lys Gly Asn 705 710 715 720 Ile Lys Glu Val Val Lys Ser Leu Pro Gly Ser Pro Ala Ile Lys Lys 725 730 735 Gly Ile Leu Gln Ser Ile Lys Ile Val Asp Glu Leu Val Lys Val Met 740 745 750 Gly Gly Arg Lys Pro Glu Ser Ile Val Val Glu Met Ala Arg Glu Asn 755 760 765 Gln Tyr Thr Asn Gln Gly Lys Ser Asn Ser Gln Gln Arg Leu Lys Arg 770 775 780 Leu Glu Lys Ser Leu Lys Glu Leu Gly Ser Lys Ile Leu Lys Glu Asn 785 790 795 800 Ile Pro Ala Lys Leu Ser Lys Ile Asp Asn Asn Ala Leu Gln Asn Asp 805 810 815 Arg Leu Tyr Leu Tyr Tyr Leu Gln Asn Gly Lys Asp Met Tyr Thr Gly 820 825 830 Asp Asp Leu Asp Ile Asp Arg Leu Ser Asn Tyr Asp Ile Asp His Ile 835 840 845 Ile Pro Gln Ala Phe Leu Lys Asp Asn Ser Ile Asp Asn Lys Val Leu 850 855 860 Val Ser Ser Ala Ser Asn Arg Gly Lys Ser Asp Asp Val Pro Ser Leu 865 870 875 880 Glu Val Val Lys Lys Arg Lys Thr Phe Trp Tyr Gln Leu Leu Lys Ser 885 890 895 Lys Leu Ile Ser Gln Arg Lys Phe Asp Asn Leu Thr Lys Ala Glu Arg 900 905 910 Gly Gly Leu Ser Pro Glu Asp Lys Ala Gly Phe Ile Gln Arg Gln Leu 915 920 925 Val Glu Thr Arg Gln Ile Thr Lys His Val Ala Arg Leu Leu Asp Glu 930 935 940 Lys Phe Asn Asn Lys Lys Asp Glu Asn Asn Arg Ala Val Arg Thr Val 945 950 955 960 Lys Ile Ile Thr Leu Lys Ser Thr Leu Val Ser Gln Phe Arg Lys Asp 965 970 975 Phe Glu Leu Tyr Lys Val Arg Glu Ile Asn Asp Phe His His Ala His 980 985 990 Asp Ala Tyr Leu Asn Ala Val Val Ala Ser Ala Leu Leu Lys Lys Tyr 995 1000 1005 Pro Lys Leu Glu Pro Glu Phe Val Tyr Gly Asp Tyr Pro Lys Tyr 1010 1015 1020 Asn Ser Phe Arg Glu Arg Lys Ser Ala Thr Glu Lys Val Tyr Phe 1025 1030 1035 Tyr Ser Asn Ile Met Asn Ile Phe Lys Lys Ser Ile Ser Leu Ala 1040 1045 1050 Asp Gly Arg Val Ile Glu Arg Pro Leu Ile Glu Val Asn Glu Glu 1055 1060 1065 Thr Gly Glu Ser Val Trp Asn Lys Glu Ser Asp Leu Ala Thr Val 1070 1075 1080 Arg Arg Val Leu Ser Tyr Pro Gln Val Asn Val Val Lys Lys Val 1085 1090 1095 Glu Glu Gln Asn His Gly Leu Asp Arg Gly Lys Pro Lys Gly Leu 1100 1105 1110 Phe Asn Ala Asn Leu Ser Ser Lys Pro Lys Pro Asn Ser Asn Glu 1115 1120 1125 Asn Leu Val Gly Ala Lys Glu Tyr Leu Asp Pro Lys Lys Tyr Gly 1130 1135 1140 Gly Tyr Ala Gly Ile Ser Asn Ser Phe Thr Val Leu Val Lys Gly 1145 1150 1155 Thr Ile Glu Lys Gly Ala Lys Lys Lys Ile Thr Asn Val Leu Glu 1160 1165 1170 Phe Gln Gly Ile Ser Ile Leu Asp Arg Ile Asn Tyr Arg Lys Asp 1175 1180 1185 Lys Leu Asn Phe Leu Leu Glu Lys Gly Tyr Lys Asp Ile Glu Leu 1190 1195 1200 Ile Ile Glu Leu Pro Lys Tyr Ser Leu Phe Glu Leu Ser Asp Gly 1205 1210 1215 Ser Arg Arg Met Leu Ala Ser Ile Leu Ser Thr Asn Asn Lys Arg 1220 1225 1230 Gly Glu Ile His Lys Gly Asn Gln Ile Phe Leu Ser Gln Lys Phe 1235 1240 1245 Val Lys Leu Leu Tyr His Ala Lys Arg Ile Ser Asn Thr Ile Asn 1250 1255 1260 Glu Asn His Arg Lys Tyr Val Glu Asn His Lys Lys Glu Phe Glu 1265 1270 1275 Glu Leu Phe Tyr Tyr Ile Leu Glu Phe Asn Glu Asn Tyr Val Gly 1280 1285 1290 Ala Lys Lys Asn Gly Lys Leu Leu Asn Ser Ala Phe Gln Ser Trp 1295 1300 1305 Gln Asn His Ser Ile Asp Glu Leu Cys Ser Ser Phe Ile Gly Pro 1310 1315 1320 Thr Gly Ser Glu Arg Lys Gly Leu Phe Glu Leu Thr Ser Arg Gly 1325 1330 1335 Ser Ala Ala Asp Phe Glu Phe Leu Gly Val Lys Ile Pro Arg Tyr 1340 1345 1350 Arg Asp Tyr Thr Pro Ser Ser Leu Leu Lys Asp Ala Thr Leu Ile 1355 1360 1365 His Gln Ser Val Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ala 1370 1375 1380 Lys Leu Gly Glu Gly 1385 <210> 558 <211> 1388 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="Streptococcus thermophilus Cas9 D10A nickase" <400> 558 Met Thr Lys Pro Tyr Ser Ile Gly Leu Ala Ile Gly Thr Asn Ser Val 1 5 10 15 Gly Trp Ala Val Thr Thr Asp Asn Tyr Lys Val Pro Ser Lys Lys Met 20 25 30 Lys Val Leu Gly Asn Thr Ser Lys Lys Tyr Ile Lys Lys Asn Leu Leu 35 40 45 Gly Val Leu Leu Phe Asp Ser Gly Ile Thr Ala Glu Gly Arg Arg Leu 50 55 60 Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Arg Asn Arg Ile Leu 65 70 75 80 Tyr Leu Gln Glu Ile Phe Ser Thr Glu Met Ala Thr Leu Asp Asp Ala 85 90 95 Phe Phe Gln Arg Leu Asp Asp Ser Phe Leu Val Pro Asp Asp Lys Arg 100 105 110 Asp Ser Lys Tyr Pro Ile Phe Gly Asn Leu Val Glu Glu Lys Ala Tyr 115 120 125 His Asp Glu Phe Pro Thr Ile Tyr His Leu Arg Lys Tyr Leu Ala Asp 130 135 140 Ser Thr Lys Lys Ala Asp Leu Arg Leu Val Tyr Leu Ala Leu Ala His 145 150 155 160 Met Ile Lys Tyr Arg Gly His Phe Leu Ile Glu Gly Glu Phe Asn Ser 165 170 175 Lys Asn Asn Asp Ile Gln Lys Asn Phe Gln Asp Phe Leu Asp Thr Tyr 180 185 190 Asn Ala Ile Phe Glu Ser Asp Leu Ser Leu Glu Asn Ser Lys Gln Leu 195 200 205 Glu Glu Ile Val Lys Asp Lys Ile Ser Lys Leu Glu Lys Lys Asp Arg 210 215 220 Ile Leu Lys Leu Phe Pro Gly Glu Lys Asn Ser Gly Ile Phe Ser Glu 225 230 235 240 Phe Leu Lys Leu Ile Val Gly Asn Gln Ala Asp Phe Arg Lys Cys Phe 245 250 255 Asn Leu Asp Glu Lys Ala Ser Leu His Phe Ser Lys Glu Ser Tyr Asp 260 265 270 Glu Asp Leu Glu Thr Leu Leu Gly Tyr Ile Gly Asp Asp Tyr Ser Asp 275 280 285 Val Phe Leu Lys Ala Lys Lys Leu Tyr Asp Ala Ile Leu Leu Ser Gly 290 295 300 Phe Leu Thr Val Thr Asp Asn Glu Thr Glu Ala Pro Leu Ser Ser Ala 305 310 315 320 Met Ile Lys Arg Tyr Asn Glu His Lys Glu Asp Leu Ala Leu Leu Lys 325 330 335 Glu Tyr Ile Arg Asn Ile Ser Leu Lys Thr Tyr Asn Glu Val Phe Lys 340 345 350 Asp Asp Thr Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Lys Thr Asn 355 360 365 Gln Glu Asp Phe Tyr Val Tyr Leu Lys Lys Leu Leu Ala Glu Phe Glu 370 375 380 Gly Ala Asp Tyr Phe Leu Glu Lys Ile Asp Arg Glu Asp Phe Leu Arg 385 390 395 400 Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro Tyr Gln Ile His Leu 405 410 415 Gln Glu Met Arg Ala Ile Leu Asp Lys Gln Ala Lys Phe Tyr Pro Phe 420 425 430 Leu Ala Lys Asn Lys Glu Arg Ile Glu Lys Ile Leu Thr Phe Arg Ile 435 440 445 Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser Asp Phe Ala Trp 450 455 460 Ser Ile Arg Lys Arg Asn Glu Lys Ile Thr Pro Trp Asn Phe Glu Asp 465 470 475 480 Val Ile Asp Lys Glu Ser Ser Ala Glu Ala Phe Ile Asn Arg Met Thr 485 490 495 Ser Phe Asp Leu Tyr Leu Pro Glu Glu Lys Val Leu Pro Lys His Ser 500 505 510 Leu Leu Tyr Glu Thr Phe Asn Val Tyr Asn Glu Leu Thr Lys Val Arg 515 520 525 Phe Ile Ala Glu Ser Met Arg Asp Tyr Gln Phe Leu Asp Ser Lys Gln 530 535 540 Lys Lys Asp Ile Val Arg Leu Tyr Phe Lys Asp Lys Arg Lys Val Thr 545 550 555 560 Asp Lys Asp Ile Ile Glu Tyr Leu His Ala Ile Tyr Gly Tyr Asp Gly 565 570 575 Ile Glu Leu Lys Gly Ile Glu Lys Gln Phe Asn Ser Ser Leu Ser Thr 580 585 590 Tyr His Asp Leu Leu Asn Ile Ile Asn Asp Lys Glu Phe Leu Asp Asp 595 600 605 Ser Ser Asn Glu Ala Ile Ile Glu Glu Ile Ile His Thr Leu Thr Ile 610 615 620 Phe Glu Asp Arg Glu Met Ile Lys Gln Arg Leu Ser Lys Phe Glu Asn 625 630 635 640 Ile Phe Asp Lys Ser Val Leu Lys Lys Leu Ser Arg Arg His Tyr Thr 645 650 655 Gly Trp Gly Lys Leu Ser Ala Lys Leu Ile Asn Gly Ile Arg Asp Glu 660 665 670 Lys Ser Gly Asn Thr Ile Leu Asp Tyr Leu Ile Asp Asp Gly Ile Ser 675 680 685 Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ala Leu Ser Phe Lys 690 695 700 Lys Lys Ile Gln Lys Ala Gln Ile Ile Gly Asp Glu Asp Lys Gly Asn 705 710 715 720 Ile Lys Glu Val Val Lys Ser Leu Pro Gly Ser Pro Ala Ile Lys Lys 725 730 735 Gly Ile Leu Gln Ser Ile Lys Ile Val Asp Glu Leu Val Lys Val Met 740 745 750 Gly Gly Arg Lys Pro Glu Ser Ile Val Val Glu Met Ala Arg Glu Asn 755 760 765 Gln Tyr Thr Asn Gln Gly Lys Ser Asn Ser Gln Gln Arg Leu Lys Arg 770 775 780 Leu Glu Lys Ser Leu Lys Glu Leu Gly Ser Lys Ile Leu Lys Glu Asn 785 790 795 800 Ile Pro Ala Lys Leu Ser Lys Ile Asp Asn Asn Ala Leu Gln Asn Asp 805 810 815 Arg Leu Tyr Leu Tyr Tyr Leu Gln Asn Gly Lys Asp Met Tyr Thr Gly 820 825 830 Asp Asp Leu Asp Ile Asp Arg Leu Ser Asn Tyr Asp Ile Asp His Ile 835 840 845 Ile Pro Gln Ala Phe Leu Lys Asp Asn Ser Ile Asp Asn Lys Val Leu 850 855 860 Val Ser Ser Ala Ser Asn Arg Gly Lys Ser Asp Asp Val Pro Ser Leu 865 870 875 880 Glu Val Val Lys Lys Arg Lys Thr Phe Trp Tyr Gln Leu Leu Lys Ser 885 890 895 Lys Leu Ile Ser Gln Arg Lys Phe Asp Asn Leu Thr Lys Ala Glu Arg 900 905 910 Gly Gly Leu Ser Pro Glu Asp Lys Ala Gly Phe Ile Gln Arg Gln Leu 915 920 925 Val Glu Thr Arg Gln Ile Thr Lys His Val Ala Arg Leu Leu Asp Glu 930 935 940 Lys Phe Asn Asn Lys Lys Asp Glu Asn Asn Arg Ala Val Arg Thr Val 945 950 955 960 Lys Ile Ile Thr Leu Lys Ser Thr Leu Val Ser Gln Phe Arg Lys Asp 965 970 975 Phe Glu Leu Tyr Lys Val Arg Glu Ile Asn Asp Phe His His Ala His 980 985 990 Asp Ala Tyr Leu Asn Ala Val Val Ala Ser Ala Leu Leu Lys Lys Tyr 995 1000 1005 Pro Lys Leu Glu Pro Glu Phe Val Tyr Gly Asp Tyr Pro Lys Tyr 1010 1015 1020 Asn Ser Phe Arg Glu Arg Lys Ser Ala Thr Glu Lys Val Tyr Phe 1025 1030 1035 Tyr Ser Asn Ile Met Asn Ile Phe Lys Lys Ser Ile Ser Leu Ala 1040 1045 1050 Asp Gly Arg Val Ile Glu Arg Pro Leu Ile Glu Val Asn Glu Glu 1055 1060 1065 Thr Gly Glu Ser Val Trp Asn Lys Glu Ser Asp Leu Ala Thr Val 1070 1075 1080 Arg Arg Val Leu Ser Tyr Pro Gln Val Asn Val Val Lys Lys Val 1085 1090 1095 Glu Glu Gln Asn His Gly Leu Asp Arg Gly Lys Pro Lys Gly Leu 1100 1105 1110 Phe Asn Ala Asn Leu Ser Ser Lys Pro Lys Pro Asn Ser Asn Glu 1115 1120 1125 Asn Leu Val Gly Ala Lys Glu Tyr Leu Asp Pro Lys Lys Tyr Gly 1130 1135 1140 Gly Tyr Ala Gly Ile Ser Asn Ser Phe Thr Val Leu Val Lys Gly 1145 1150 1155 Thr Ile Glu Lys Gly Ala Lys Lys Lys Ile Thr Asn Val Leu Glu 1160 1165 1170 Phe Gln Gly Ile Ser Ile Leu Asp Arg Ile Asn Tyr Arg Lys Asp 1175 1180 1185 Lys Leu Asn Phe Leu Leu Glu Lys Gly Tyr Lys Asp Ile Glu Leu 1190 1195 1200 Ile Ile Glu Leu Pro Lys Tyr Ser Leu Phe Glu Leu Ser Asp Gly 1205 1210 1215 Ser Arg Arg Met Leu Ala Ser Ile Leu Ser Thr Asn Asn Lys Arg 1220 1225 1230 Gly Glu Ile His Lys Gly Asn Gln Ile Phe Leu Ser Gln Lys Phe 1235 1240 1245 Val Lys Leu Leu Tyr His Ala Lys Arg Ile Ser Asn Thr Ile Asn 1250 1255 1260 Glu Asn His Arg Lys Tyr Val Glu Asn His Lys Lys Glu Phe Glu 1265 1270 1275 Glu Leu Phe Tyr Tyr Ile Leu Glu Phe Asn Glu Asn Tyr Val Gly 1280 1285 1290 Ala Lys Lys Asn Gly Lys Leu Leu Asn Ser Ala Phe Gln Ser Trp 1295 1300 1305 Gln Asn His Ser Ile Asp Glu Leu Cys Ser Ser Phe Ile Gly Pro 1310 1315 1320 Thr Gly Ser Glu Arg Lys Gly Leu Phe Glu Leu Thr Ser Arg Gly 1325 1330 1335 Ser Ala Ala Asp Phe Glu Phe Leu Gly Val Lys Ile Pro Arg Tyr 1340 1345 1350 Arg Asp Tyr Thr Pro Ser Ser Leu Leu Lys Asp Ala Thr Leu Ile 1355 1360 1365 His Gln Ser Val Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ala 1370 1375 1380 Lys Leu Gly Glu Gly 1385 <210> 559 <211> 1368 <212> PRT <213> Staphylococcus aureus <220> <221> source <223> /note="Staphylococcus aureus Cas9" <400> 559 Met Asp Lys Lys Tyr Ser Ile Gly Leu Asp Ile Gly Thr Asn Ser Val 1 5 10 15 Gly Trp Ala Val Ile Thr Asp Glu Tyr Lys Val Pro Ser Lys Lys Phe 20 25 30 Lys Val Leu Gly Asn Thr Asp Arg His Ser Ile Lys Lys Asn Leu Ile 35 40 45 Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr Ala Glu Ala Thr Arg Leu 50 55 60 Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Lys Asn Arg Ile Cys 65 70 75 80 Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met Ala Lys Val Asp Asp Ser 85 90 95 Phe Phe His Arg Leu Glu Glu Ser Phe Leu Val Glu Glu Asp Lys Lys 100 105 110 His Glu Arg His Pro Ile Phe Gly Asn Ile Val Asp Glu Val Ala Tyr 115 120 125 His Glu Lys Tyr Pro Thr Ile Tyr His Leu Arg Lys Lys Leu Val Asp 130 135 140 Ser Thr Asp Lys Ala Asp Leu Arg Leu Ile Tyr Leu Ala Leu Ala His 145 150 155 160 Met Ile Lys Phe Arg Gly His Phe Leu Ile Glu Gly Asp Leu Asn Pro 165 170 175 Asp Asn Ser Asp Val Asp Lys Leu Phe Ile Gln Leu Val Gln Thr Tyr 180 185 190 Asn Gln Leu Phe Glu Asn Pro Ile Asn Ala Ser Gly Val Asp Ala 195 200 205 Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys Ser Arg Arg Leu Glu Asn 210 215 220 Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys Asn Gly Leu Phe Gly Asn 225 230 235 240 Leu Ile Ala Leu Ser Leu Gly Leu Thr Pro Asn Phe Lys Ser Asn Phe 245 250 255 Asp Leu Ala Glu Asp Ala Lys Leu Gln Leu Ser Lys Asp Thr Tyr Asp 260 265 270 Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile Gly Asp Gln Tyr Ala Asp 275 280 285 Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp Ala Ile Leu Leu Ser Asp 290 295 300 Ile Leu Arg Val Asn Thr Glu Ile Thr Lys Ala Pro Leu Ser Ala Ser 305 310 315 320 Met Ile Lys Arg Tyr Asp Glu His His Gln Asp Leu Thr Leu Leu Lys 325 330 335 Ala Leu Val Arg Gln Gln Leu Pro Glu Lys Tyr Lys Glu Ile Phe Phe 340 345 350 Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Gly Ala Ser 355 360 365 Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro Ile Leu Glu Lys Met Asp 370 375 380 Gly Thr Glu Glu Leu Leu Val Lys Leu Asn Arg Glu Asp Leu Leu Arg 385 390 395 400 Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro His Gln Ile His Leu 405 410 415 Gly Glu Leu His Ala Ile Leu Arg Arg Gln Glu Asp Phe Tyr Pro Phe 420 425 430 Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys Ile Leu Thr Phe Arg Ile 435 440 445 Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser Arg Phe Ala Trp 450 455 460 Met Thr Arg Lys Ser Glu Glu Thr Ile Thr Pro Trp Asn Phe Glu Glu 465 470 475 480 Val Val Asp Lys Gly Ala Ser Ala Gln Ser Phe Ile Glu Arg Met Thr 485 490 495 Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys Val Leu Pro Lys His Ser 500 505 510 Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn Glu Leu Thr Lys Val Lys 515 520 525 Tyr Val Thr Glu Gly Met Arg Lys Pro Ala Phe Leu Ser Gly Glu Gln 530 535 540 Lys Lys Ala Ile Val Asp Leu Leu Phe Lys Thr Asn Arg Lys Val Thr 545 550 555 560 Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys Lys Ile Glu Cys Phe Asp 565 570 575 Ser Val Glu Ile Ser Gly Val Glu Asp Arg Phe Asn Ala Ser Leu Gly 580 585 590 Thr Tyr His Asp Leu Leu Lys Ile Ile Lys Asp Lys Asp Phe Leu Asp 595 600 605 Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp Ile Val Leu Thr Leu Thr 610 615 620 Leu Phe Glu Asp Arg Glu Met Ile Glu Glu Arg Leu Lys Thr Tyr Ala 625 630 635 640 His Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys Arg Arg Arg Tyr 645 650 655 Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn Gly Ile Arg Asp 660 665 670 Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys Ser Asp Gly Phe 675 680 685 Ala Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ser Leu Thr Phe 690 695 700 Lys Glu Asp Ile Gln Lys Ala Gln Val Ser Gly Gln Gly Asp Ser Leu 705 710 715 720 His Glu His Ile Ala Asn Leu Ala Gly Ser Pro Ala Ile Lys Lys Gly 725 730 735 Ile Leu Gln Thr Val Lys Val Val Asp Glu Leu Val Lys Val Met Gly 740 745 750 Arg His Lys Pro Glu Asn Ile Val Ile Glu Met Ala Arg Glu Asn Gln 755 760 765 Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg Glu Arg Met Lys Arg Ile 770 775 780 Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln Ile Leu Lys Glu His Pro 785 790 795 800 Val Glu Asn Thr Gln Leu Gln Asn Glu Lys Leu Tyr Leu Tyr Tyr Leu 805 810 815 Gln Asn Gly Arg Asp Met Tyr Val Asp Gln Glu Leu Asp Ile Asn Arg 820 825 830 Leu Ser Asp Tyr Asp Val Asp His Ile Val Pro Gln Ser Phe Leu Lys 835 840 845 Asp Asp Ser Ile Asp Asn Lys Val Leu Thr Arg Ser Asp Lys Asn Arg 850 855 860 Gly Lys Ser Asp Asn Val Pro Ser Glu Glu Val Val Lys Lys Met Lys 865 870 875 880 Asn Tyr Trp Arg Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys 885 890 895 Phe Asp Asn Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp 900 905 910 Lys Ala Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr 915 920 925 Lys His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp 930 935 940 Glu Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr Leu Lys Ser 945 950 955 960 Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys Val Arg 965 970 975 Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu Asn Ala Val 980 985 990 Val Gly Thr Ala Leu Ile Lys Lys Tyr Pro Lys Leu Glu Ser Glu Phe 995 1000 1005 Val Tyr Gly Asp Tyr Lys Val Tyr Asp Val Arg Lys Met Ile Ala 1010 1015 1020 Lys Ser Glu Gln Glu Ile Gly Lys Ala Thr Ala Lys Tyr Phe Phe 1025 1030 1035 Tyr Ser Asn Ile Met Asn Phe Phe Lys Thr Glu Ile Thr Leu Ala 1040 1045 1050 Asn Gly Glu Ile Arg Lys Arg Pro Leu Ile Glu Thr Asn Gly Glu 1055 1060 1065 Thr Gly Glu Ile Val Trp Asp Lys Gly Arg Asp Phe Ala Thr Val 1070 1075 1080 Arg Lys Val Leu Ser Met Pro Gln Val Asn Ile Val Lys Lys Thr 1085 1090 1095 Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro Lys 1100 1105 1110 Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 1115 1120 1125 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val 1130 1135 1140 Leu Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys 1145 1150 1155 Ser Val Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser 1160 1165 1170 Phe Glu Lys Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys 1175 1180 1185 Glu Val Lys Lys Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu 1190 1195 1200 Phe Glu Leu Glu Asn Gly Arg Lys Arg Met Leu Ala Ser Ala Gly 1205 1210 1215 Glu Leu Gln Lys Gly Asn Glu Leu Ala Leu Pro Ser Lys Tyr Val 1220 1225 1230 Asn Phe Leu Tyr Leu Ala Ser His Tyr Glu Lys Leu Lys Gly Ser 1235 1240 1245 Pro Glu Asp Asn Glu Gln Lys Gln Leu Phe Val Glu Gln His Lys 1250 1255 1260 His Tyr Leu Asp Glu Ile Ile Glu Gln Ile Ser Glu Phe Ser Lys 1265 1270 1275 Arg Val Ile Leu Ala Asp Ala Asn Leu Asp Lys Val Leu Ser Ala 1280 1285 1290 Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu Gln Ala Glu Asn 1295 1300 1305 Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala Pro Ala Ala 1310 1315 1320 Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Arg Tyr Thr Ser 1325 1330 1335 Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile Thr 1340 1345 1350 Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 1355 1360 1365 <210> 560 <211> 1368 <212> PRT <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polypeptide" <220> <221> source <223> /note="Staphylococcus aureus Cas9 D10A nickase" <400> 560 Met Asp Lys Lys Tyr Ser Ile Gly Leu Ala Ile Gly Thr Asn Ser Val 1 5 10 15 Gly Trp Ala Val Ile Thr Asp Glu Tyr Lys Val Pro Ser Lys Lys Phe 20 25 30 Lys Val Leu Gly Asn Thr Asp Arg His Ser Ile Lys Lys Asn Leu Ile 35 40 45 Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr Ala Glu Ala Thr Arg Leu 50 55 60 Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Lys Asn Arg Ile Cys 65 70 75 80 Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met Ala Lys Val Asp Asp Ser 85 90 95 Phe Phe His Arg Leu Glu Glu Ser Phe Leu Val Glu Glu Asp Lys Lys 100 105 110 His Glu Arg His Pro Ile Phe Gly Asn Ile Val Asp Glu Val Ala Tyr 115 120 125 His Glu Lys Tyr Pro Thr Ile Tyr His Leu Arg Lys Lys Leu Val Asp 130 135 140 Ser Thr Asp Lys Ala Asp Leu Arg Leu Ile Tyr Leu Ala Leu Ala His 145 150 155 160 Met Ile Lys Phe Arg Gly His Phe Leu Ile Glu Gly Asp Leu Asn Pro 165 170 175 Asp Asn Ser Asp Val Asp Lys Leu Phe Ile Gln Leu Val Gln Thr Tyr 180 185 190 Asn Gln Leu Phe Glu Asn Pro Ile Asn Ala Ser Gly Val Asp Ala 195 200 205 Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys Ser Arg Arg Leu Glu Asn 210 215 220 Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys Asn Gly Leu Phe Gly Asn 225 230 235 240 Leu Ile Ala Leu Ser Leu Gly Leu Thr Pro Asn Phe Lys Ser Asn Phe 245 250 255 Asp Leu Ala Glu Asp Ala Lys Leu Gln Leu Ser Lys Asp Thr Tyr Asp 260 265 270 Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile Gly Asp Gln Tyr Ala Asp 275 280 285 Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp Ala Ile Leu Leu Ser Asp 290 295 300 Ile Leu Arg Val Asn Thr Glu Ile Thr Lys Ala Pro Leu Ser Ala Ser 305 310 315 320 Met Ile Lys Arg Tyr Asp Glu His His Gln Asp Leu Thr Leu Leu Lys 325 330 335 Ala Leu Val Arg Gln Gln Leu Pro Glu Lys Tyr Lys Glu Ile Phe Phe 340 345 350 Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Gly Ala Ser 355 360 365 Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro Ile Leu Glu Lys Met Asp 370 375 380 Gly Thr Glu Glu Leu Leu Val Lys Leu Asn Arg Glu Asp Leu Leu Arg 385 390 395 400 Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro His Gln Ile His Leu 405 410 415 Gly Glu Leu His Ala Ile Leu Arg Arg Gln Glu Asp Phe Tyr Pro Phe 420 425 430 Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys Ile Leu Thr Phe Arg Ile 435 440 445 Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser Arg Phe Ala Trp 450 455 460 Met Thr Arg Lys Ser Glu Glu Thr Ile Thr Pro Trp Asn Phe Glu Glu 465 470 475 480 Val Val Asp Lys Gly Ala Ser Ala Gln Ser Phe Ile Glu Arg Met Thr 485 490 495 Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys Val Leu Pro Lys His Ser 500 505 510 Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn Glu Leu Thr Lys Val Lys 515 520 525 Tyr Val Thr Glu Gly Met Arg Lys Pro Ala Phe Leu Ser Gly Glu Gln 530 535 540 Lys Lys Ala Ile Val Asp Leu Leu Phe Lys Thr Asn Arg Lys Val Thr 545 550 555 560 Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys Lys Ile Glu Cys Phe Asp 565 570 575 Ser Val Glu Ile Ser Gly Val Glu Asp Arg Phe Asn Ala Ser Leu Gly 580 585 590 Thr Tyr His Asp Leu Leu Lys Ile Ile Lys Asp Lys Asp Phe Leu Asp 595 600 605 Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp Ile Val Leu Thr Leu Thr 610 615 620 Leu Phe Glu Asp Arg Glu Met Ile Glu Glu Arg Leu Lys Thr Tyr Ala 625 630 635 640 His Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys Arg Arg Arg Tyr 645 650 655 Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn Gly Ile Arg Asp 660 665 670 Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys Ser Asp Gly Phe 675 680 685 Ala Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ser Leu Thr Phe 690 695 700 Lys Glu Asp Ile Gln Lys Ala Gln Val Ser Gly Gln Gly Asp Ser Leu 705 710 715 720 His Glu His Ile Ala Asn Leu Ala Gly Ser Pro Ala Ile Lys Lys Gly 725 730 735 Ile Leu Gln Thr Val Lys Val Val Asp Glu Leu Val Lys Val Met Gly 740 745 750 Arg His Lys Pro Glu Asn Ile Val Ile Glu Met Ala Arg Glu Asn Gln 755 760 765 Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg Glu Arg Met Lys Arg Ile 770 775 780 Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln Ile Leu Lys Glu His Pro 785 790 795 800 Val Glu Asn Thr Gln Leu Gln Asn Glu Lys Leu Tyr Leu Tyr Tyr Leu 805 810 815 Gln Asn Gly Arg Asp Met Tyr Val Asp Gln Glu Leu Asp Ile Asn Arg 820 825 830 Leu Ser Asp Tyr Asp Val Asp His Ile Val Pro Gln Ser Phe Leu Lys 835 840 845 Asp Asp Ser Ile Asp Asn Lys Val Leu Thr Arg Ser Asp Lys Asn Arg 850 855 860 Gly Lys Ser Asp Asn Val Pro Ser Glu Glu Val Val Lys Lys Met Lys 865 870 875 880 Asn Tyr Trp Arg Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys 885 890 895 Phe Asp Asn Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp 900 905 910 Lys Ala Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr 915 920 925 Lys His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp 930 935 940 Glu Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr Leu Lys Ser 945 950 955 960 Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys Val Arg 965 970 975 Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu Asn Ala Val 980 985 990 Val Gly Thr Ala Leu Ile Lys Lys Tyr Pro Lys Leu Glu Ser Glu Phe 995 1000 1005 Val Tyr Gly Asp Tyr Lys Val Tyr Asp Val Arg Lys Met Ile Ala 1010 1015 1020 Lys Ser Glu Gln Glu Ile Gly Lys Ala Thr Ala Lys Tyr Phe Phe 1025 1030 1035 Tyr Ser Asn Ile Met Asn Phe Phe Lys Thr Glu Ile Thr Leu Ala 1040 1045 1050 Asn Gly Glu Ile Arg Lys Arg Pro Leu Ile Glu Thr Asn Gly Glu 1055 1060 1065 Thr Gly Glu Ile Val Trp Asp Lys Gly Arg Asp Phe Ala Thr Val 1070 1075 1080 Arg Lys Val Leu Ser Met Pro Gln Val Asn Ile Val Lys Lys Thr 1085 1090 1095 Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro Lys 1100 1105 1110 Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 1115 1120 1125 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val 1130 1135 1140 Leu Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys 1145 1150 1155 Ser Val Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser 1160 1165 1170 Phe Glu Lys Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys 1175 1180 1185 Glu Val Lys Lys Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu 1190 1195 1200 Phe Glu Leu Glu Asn Gly Arg Lys Arg Met Leu Ala Ser Ala Gly 1205 1210 1215 Glu Leu Gln Lys Gly Asn Glu Leu Ala Leu Pro Ser Lys Tyr Val 1220 1225 1230 Asn Phe Leu Tyr Leu Ala Ser His Tyr Glu Lys Leu Lys Gly Ser 1235 1240 1245 Pro Glu Asp Asn Glu Gln Lys Gln Leu Phe Val Glu Gln His Lys 1250 1255 1260 His Tyr Leu Asp Glu Ile Ile Glu Gln Ile Ser Glu Phe Ser Lys 1265 1270 1275 Arg Val Ile Leu Ala Asp Ala Asn Leu Asp Lys Val Leu Ser Ala 1280 1285 1290 Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu Gln Ala Glu Asn 1295 1300 1305 Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala Pro Ala Ala 1310 1315 1320 Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Arg Tyr Thr Ser 1325 1330 1335 Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile Thr 1340 1345 1350 Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 1355 1360 1365 <210> 561 <211> 1300 <212> PRT <213> Francisella novicida <220> <221> source <223> /note="Francisella novicida Cas12a" <400> 561 Met Ser Ile Tyr Gln Glu Phe Val Asn Lys Tyr Ser Leu Ser Lys Thr 1 5 10 15 Leu Arg Phe Glu Leu Ile Pro Gln Gly Lys Thr Leu Glu Asn Ile Lys 20 25 30 Ala Arg Gly Leu Ile Leu Asp Asp Glu Lys Arg Ala Lys Asp Tyr Lys 35 40 45 Lys Ala Lys Gln Ile Ile Asp Lys Tyr His Gln Phe Phe Ile Glu Glu 50 55 60 Ile Leu Ser Ser Val Cys Ile Ser Glu Asp Leu Leu Gln Asn Tyr Ser 65 70 75 80 Asp Val Tyr Phe Lys Leu Lys Lys Ser Asp Asp Asp Asn Leu Gln Lys 85 90 95 Asp Phe Lys Ser Ala Lys Asp Thr Ile Lys Lys Gln Ile Ser Glu Tyr 100 105 110 Ile Lys Asp Ser Glu Lys Phe Lys Asn Leu Phe Asn Gln Asn Leu Ile 115 120 125 Asp Ala Lys Lys Gly Gln Glu Ser Asp Leu Ile Leu Trp Leu Lys Gln 130 135 140 Ser Lys Asp Asn Gly Ile Glu Leu Phe Lys Ala Asn Ser Asp Ile Thr 145 150 155 160 Asp Ile Asp Glu Ala Leu Glu Ile Ile Lys Ser Phe Lys Gly Trp Thr 165 170 175 Thr Tyr Phe Lys Gly Phe His Glu Asn Arg Lys Asn Val Tyr Ser Ser 180 185 190 Asn Asp Ile Pro Thr Ser Ile Ile Tyr Arg Ile Val Asp Asp Asn Leu 195 200 205 Pro Lys Phe Leu Glu Asn Lys Ala Lys Tyr Glu Ser Leu Lys Asp Lys 210 215 220 Ala Pro Glu Ala Ile Asn Tyr Glu Gln Ile Lys Lys Asp Leu Ala Glu 225 230 235 240 Glu Leu Thr Phe Asp Ile Asp Tyr Lys Thr Ser Glu Val Asn Gln Arg 245 250 255 Val Phe Ser Leu Asp Glu Val Phe Glu Ile Ala Asn Phe Asn Asn Tyr 260 265 270 Leu Asn Gln Ser Gly Ile Thr Lys Phe Asn Thr Ile Ile Gly Gly Lys 275 280 285 Phe Val Asn Gly Glu Asn Thr Lys Arg Lys Gly Ile Asn Glu Tyr Ile 290 295 300 Asn Leu Tyr Ser Gln Gln Ile Asn Asp Lys Thr Leu Lys Lys Tyr Lys 305 310 315 320 Met Ser Val Leu Phe Lys Gln Ile Leu Ser Asp Thr Glu Ser Lys Ser 325 330 335 Phe Val Ile Asp Lys Leu Glu Asp Asp Ser Asp Val Val Thr Thr Met 340 345 350 Gln Ser Phe Tyr Glu Gln Ile Ala Ala Phe Lys Thr Val Glu Glu Lys 355 360 365 Ser Ile Lys Glu Thr Leu Ser Leu Leu Phe Asp Asp Leu Lys Ala Gln 370 375 380 Lys Leu Asp Leu Ser Lys Ile Tyr Phe Lys Asn Asp Lys Ser Leu Thr 385 390 395 400 Asp Leu Ser Gln Gln Val Phe Asp Asp Tyr Ser Val Ile Gly Thr Ala 405 410 415 Val Leu Glu Tyr Ile Thr Gln Gln Ile Ala Pro Lys Asn Leu Asp Asn 420 425 430 Pro Ser Lys Lys Glu Gln Glu Leu Ile Ala Lys Lys Thr Glu Lys Ala 435 440 445 Lys Tyr Leu Ser Leu Glu Thr Ile Lys Leu Ala Leu Glu Glu Phe Asn 450 455 460 Lys His Arg Asp Ile Asp Lys Gln Cys Arg Phe Glu Glu Ile Leu Ala 465 470 475 480 Asn Phe Ala Ala Ile Pro Met Ile Phe Asp Glu Ile Ala Gln Asn Lys 485 490 495 Asp Asn Leu Ala Gln Ile Ser Ile Lys Tyr Gln Asn Gln Gly Lys Lys 500 505 510 Asp Leu Leu Gln Ala Ser Ala Glu Asp Asp Val Lys Ala Ile Lys Asp 515 520 525 Leu Leu Asp Gln Thr Asn Asn Leu Leu His Lys Leu Lys Ile Phe His 530 535 540 Ile Ser Gln Ser Glu Asp Lys Ala Asn Ile Leu Asp Lys Asp Glu His 545 550 555 560 Phe Tyr Leu Val Phe Glu Glu Cys Tyr Phe Glu Leu Ala Asn Ile Val 565 570 575 Pro Leu Tyr Asn Lys Ile Arg Asn Tyr Ile Thr Gln Lys Pro Tyr Ser 580 585 590 Asp Glu Lys Phe Lys Leu Asn Phe Glu Asn Ser Thr Leu Ala Asn Gly 595 600 605 Trp Asp Lys Asn Lys Glu Pro Asp Asn Thr Ala Ile Leu Phe Ile Lys 610 615 620 Asp Asp Lys Tyr Tyr Leu Gly Val Met Asn Lys Lys Asn Asn Lys Ile 625 630 635 640 Phe Asp Asp Lys Ala Ile Lys Glu Asn Lys Gly Glu Gly Tyr Lys Lys 645 650 655 Ile Val Tyr Lys Leu Leu Pro Gly Ala Asn Lys Met Leu Pro Lys Val 660 665 670 Phe Phe Ser Ala Lys Ser Ile Lys Phe Tyr Asn Pro Ser Glu Asp Ile 675 680 685 Leu Arg Ile Arg Asn His Ser Thr His Thr Lys Asn Gly Ser Pro Gln 690 695 700 Lys Gly Tyr Glu Lys Phe Glu Phe Asn Ile Glu Asp Cys Arg Lys Phe 705 710 715 720 Ile Asp Phe Tyr Lys Gln Ser Ile Ser Lys His Pro Glu Trp Lys Asp 725 730 735 Phe Gly Phe Arg Phe Ser Asp Thr Gln Arg Tyr Asn Ser Ile Asp Glu 740 745 750 Phe Tyr Arg Glu Val Glu Asn Gln Gly Tyr Lys Leu Thr Phe Glu Asn 755 760 765 Ile Ser Glu Ser Tyr Ile Asp Ser Val Val Asn Gln Gly Lys Leu Tyr 770 775 780 Leu Phe Gln Ile Tyr Asn Lys Asp Phe Ser Ala Tyr Ser Lys Gly Arg 785 790 795 800 Pro Asn Leu His Thr Leu Tyr Trp Lys Ala Leu Phe Asp Glu Arg Asn 805 810 815 Leu Gln Asp Val Val Tyr Lys Leu Asn Gly Glu Ala Glu Leu Phe Tyr 820 825 830 Arg Lys Gln Ser Ile Pro Lys Lys Ile Thr His Pro Ala Lys Glu Ala 835 840 845 Ile Ala Asn Lys Asn Lys Asp Asn Pro Lys Lys Glu Ser Val Phe Glu 850 855 860 Tyr Asp Leu Ile Lys Asp Lys Arg Phe Thr Glu Asp Lys Phe Phe Phe 865 870 875 880 His Cys Pro Ile Thr Ile Asn Phe Lys Ser Ser Gly Ala Asn Lys Phe 885 890 895 Asn Asp Glu Ile Asn Leu Leu Leu Lys Glu Lys Ala Asn Asp Val His 900 905 910 Ile Leu Ser Ile Asp Arg Gly Glu Arg His Leu Ala Tyr Tyr Thr Leu 915 920 925 Val Asp Gly Lys Gly Asn Ile Ile Lys Gln Asp Thr Phe Asn Ile Ile 930 935 940 Gly Asn Asp Arg Met Lys Thr Asn Tyr His Asp Lys Leu Ala Ala Ile 945 950 955 960 Glu Lys Asp Arg Asp Ser Ala Arg Lys Asp Trp Lys Lys Ile Asn Asn 965 970 975 Ile Lys Glu Met Lys Glu Gly Tyr Leu Ser Gln Val Val His Glu Ile 980 985 990 Ala Lys Leu Val Ile Glu Tyr Asn Ala Ile Val Val Phe Glu Asp Leu 995 1000 1005 Asn Phe Gly Phe Lys Arg Gly Arg Phe Lys Val Glu Lys Gln Val 1010 1015 1020 Tyr Gln Lys Leu Glu Lys Met Leu Ile Glu Lys Leu Asn Tyr Leu 1025 1030 1035 Val Phe Lys Asp Asn Glu Phe Asp Lys Thr Gly Gly Val Leu Arg 1040 1045 1050 Ala Tyr Gln Leu Thr Ala Pro Phe Glu Thr Phe Lys Lys Met Gly 1055 1060 1065 Lys Gln Thr Gly Ile Ile Tyr Tyr Val Pro Ala Gly Phe Thr Ser 1070 1075 1080 Lys Ile Cys Pro Val Thr Gly Phe Val Asn Gln Leu Tyr Pro Lys 1085 1090 1095 Tyr Glu Ser Val Ser Lys Ser Gln Glu Phe Phe Ser Lys Phe Asp 1100 1105 1110 Lys Ile Cys Tyr Asn Leu Asp Lys Gly Tyr Phe Glu Phe Ser Phe 1115 1120 1125 Asp Tyr Lys Asn Phe Gly Asp Lys Ala Ala Lys Gly Lys Trp Thr 1130 1135 1140 Ile Ala Ser Phe Gly Ser Arg Leu Ile Asn Phe Arg Asn Ser Asp 1145 1150 1155 Lys Asn His Asn Trp Asp Thr Arg Glu Val Tyr Pro Thr Lys Glu 1160 1165 1170 Leu Glu Lys Leu Leu Lys Asp Tyr Ser Ile Glu Tyr Gly His Gly 1175 1180 1185 Glu Cys Ile Lys Ala Ala Ile Cys Gly Glu Ser Asp Lys Lys Phe 1190 1195 1200 Phe Ala Lys Leu Thr Ser Val Leu Asn Thr Ile Leu Gln Met Arg 1205 1210 1215 Asn Ser Lys Thr Gly Thr Glu Leu Asp Tyr Leu Ile Ser Pro Val 1220 1225 1230 Ala Asp Val Asn Gly Asn Phe Phe Asp Ser Arg Gln Ala Pro Lys 1235 1240 1245 Asn Met Pro Gln Asp Ala Asp Ala Asn Gly Ala Tyr His Ile Gly 1250 1255 1260 Leu Lys Gly Leu Met Leu Leu Gly Arg Ile Lys Asn Asn Gln Glu 1265 1270 1275 Gly Lys Lys Leu Asn Leu Val Ile Lys Asn Glu Glu Tyr Phe Glu 1280 1285 1290 Phe Val Gln Asn Arg Asn Asn 1295 1300 <210> 562 <211> 65 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN001101 genetic locus" <400> 562 accaaagatg atattttctt taatggtgcc aggcataatc caggaaaact gagaacagaa 60 tgaaa 65 <210> 563 <211> 25 <212> DNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic oligonucleotide" <220> <221> source <223> /note="SGN001101 target sequence" <400> 563 atattttctt taatggtgcc aggca 25 <210> 564 <211> 130 <212> RNA <213> artificial sequence <220> <221> source <223> /note="Description of Artificial Sequence: Synthetic polynucleotide" <220> <221> source <223> /note="SGN001101 sgRNA sequence" <400> 564 auauuuucuu uaauggugcc aggcagucau aguuccauua aagccaaaag uggcuuugau 60 120 uuccccccau 130

Claims (211)

An isolated amino acid sequence comprising an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 407, 399, 405, 1-10, 400-404, 406, and 408-441 and having deaminase activity. polypeptide. A nucleic acid molecule comprising a polynucleotide encoding a deaminase polypeptide, wherein the deaminase is:
a) has at least 80% sequence identity to any one of SEQ ID NOs: 451, 449, 443, 11-20, 444-448, 450 and 452-485, or
b) encoding an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 407, 399, 405, 1-10, 400-404, 406, and 408-441
which is encoded by a nucleotide sequence
nucleic acid molecule. 3. The nucleic acid molecule of claim 2, further comprising a heterologous promoter operably linked to said polynucleotide. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the polypeptide of claim 1 or the nucleic acid molecule of claim 2 or 3. A fusion protein comprising a DNA-binding polypeptide and a deaminase having at least 90% sequence identity to any one of SEQ ID NOs: 407, 399, 405, 1-10, 400-404, 406, and 408-441. 6. The fusion protein according to claim 5, wherein the deaminase is an adenine deaminase. 7. The fusion protein of claim 5 or 6, wherein the DNA-binding polypeptide is a meganuclease, zinc finger fusion protein or TALEN. 7. The fusion protein of claim 5 or 6, wherein the DNA-binding polypeptide is an RNA-guided, DNA-binding polypeptide. 9. The fusion protein of claim 8, wherein the RNA-guided, DNA-binding polypeptide is an RNA-guided nuclease (RGN) polypeptide. 10. The fusion protein of claim 9, wherein the RGN is a type II CRISPR-Cas polypeptide. 10. The fusion protein of claim 9, wherein the RGN is a type V CRISPR-Cas polypeptide. 12. The fusion protein according to any one of claims 9 to 11, wherein the RGN is an RGN nickase. 10. The fusion protein of claim 9, wherein the RGN has an amino acid sequence with at least 95% sequence identity to any one of SEQ ID NOs: 41, 60, 366 and 368. 13. The fusion protein of claim 12, wherein the RGN nickase is any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398. 15. The fusion protein according to any one of claims 5 to 14, further comprising at least one nuclear localization signal (NLS). A nucleic acid molecule comprising a polynucleotide encoding a DNA-binding polypeptide and a fusion protein comprising a deaminase, wherein the deaminase comprises:
a) has at least 80% sequence identity to any one of SEQ ID NOs: 451, 449, 443, 11-20, 444-448, 450 and 452-485, or
b) encoding an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 407, 399, 405, 1-10, 400-404, 406, and 408-441
which is encoded by a nucleotide sequence
nucleic acid molecule. 17. The nucleic acid molecule of claim 16, wherein the deaminase is an adenine deaminase. 18. The nucleic acid molecule of claim 16 or 17, wherein the DNA-binding polypeptide is a meganuclease, zinc finger fusion protein or TALEN. 18. The nucleic acid molecule of claim 16 or 17, wherein the DNA-binding polypeptide is an RNA-guided, DNA-binding polypeptide. 20. The nucleic acid molecule of claim 19, wherein the RNA-guided, DNA-binding polypeptide is an RNA-guided nuclease (RGN) polypeptide. 21. The nucleic acid molecule of claim 20, wherein the RGN is a type II CRISPR-Cas polypeptide. 21. The nucleic acid molecule of claim 20, wherein the RGN is a type V CRISPR-Cas polypeptide. 21. The nucleic acid molecule of claim 20, wherein the RGN is an RGN nickase. 21. The nucleic acid molecule of claim 20, wherein the RGN has an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 41, 60, 366 and 368. 24. The nucleic acid molecule of claim 23, wherein the RGN nickase is any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398. 26. The nucleic acid molecule according to any one of claims 16 to 25, wherein the polynucleotide encoding the fusion protein is operably linked at its 5' end to a heterologous promoter. 27. The nucleic acid molecule according to any one of claims 16 to 26, wherein the polynucleotide encoding the fusion protein is operably linked at its 3' end to a heterologous terminator. 28. The nucleic acid molecule of any one of claims 16-27, wherein the fusion protein comprises one or more nuclear localization signals. 29. The nucleic acid molecule according to any one of claims 16 to 28, wherein the fusion protein is codon optimized for expression in eukaryotic cells. 29. The nucleic acid molecule according to any one of claims 16 to 28, wherein the fusion protein is codon optimized for expression in prokaryotic cells. A vector comprising the nucleic acid molecule of any one of claims 16 to 30. 32. The vector of claim 31, further comprising at least one nucleotide sequence encoding a guide RNA (gRNA) capable of hybridizing to the target sequence. 33. The vector according to claim 32, wherein the gRNA is a single guide RNA. 33. The vector according to claim 32, wherein the gRNA is a double guide RNA. A cell comprising the fusion protein of any one of claims 5 to 15, the nucleic acid molecule of any one of claims 16 to 30, or the vector of any one of claims 31 to 34. A cell comprising the fusion protein of any one of claims 5 to 15 and further comprising a guide RNA. A method for producing a fusion protein comprising culturing the cell of claim 35 or 36 under conditions in which the fusion protein is expressed. A fusion protein comprising introducing the nucleic acid molecule of any one of claims 16 to 30 or the vector of any one of claims 31 to 34 into a cell and culturing the cell under conditions in which the fusion protein is expressed. How to manufacture. 39. The method of claim 37 or 38, further comprising purifying the fusion protein. A nucleic acid molecule comprising an expression cassette encoding the nucleic acid molecule of any one of claims 16 to 30 and a guide RNA, or the vector of any one of claims 31 to 34 is introduced into a cell, and the cell is converted into a fusion protein and culturing under conditions in which the gRNA is expressed to form the RGN-fusion ribonucleoprotein complex. 41. The method of claim 40, further comprising purifying the RGN fusion ribonucleoprotein complex. A system for modifying a target DNA molecule comprising a target DNA sequence, comprising:
The system
a) an RNA-guided nuclease polypeptide (RGN) and a deaminase, wherein the deaminase is SEQ ID NOs: 407, 399, 405, 1-10, 400-404, 406, and 408-441 a fusion protein having an amino acid sequence having at least 90% sequence identity to any one of, or a nucleotide sequence encoding the fusion protein; and
b) one or more guide RNAs capable of hybridizing to the target DNA sequence, or one or more nucleotide sequences encoding one or more guide RNAs (gRNAs)
contains;
Wherein the one or more guide RNAs are capable of forming a complex with the fusion protein to direct the fusion protein to bind to the target DNA sequence and modify the target DNA molecule.
system. 43. The system of claim 42, wherein at least one of the nucleotide sequence encoding the one or more guide RNAs and the nucleotide sequence encoding the fusion protein is operably linked to a promoter heterologous to the nucleotide sequence. 44. The system of claim 42 or 43, wherein the target DNA sequence is a eukaryotic target DNA sequence. 45. The system of any one of claims 42-44, wherein the target DNA sequence is located adjacent to a protospacer adjacent motif (PAM) recognized by RGN. 46. The system of any one of claims 42-45, wherein the target DNA molecule is within a cell. 47. The system of any one of claims 42-46, wherein the RGN of the fusion protein is a type II CRISPR-Cas polypeptide. 47. The system of any one of claims 42-46, wherein the RGN of the fusion protein is a type V CRISPR-Cas polypeptide. 47. The system of any one of claims 42-46, wherein the RGN of the fusion protein has an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 41, 60, 366, or 368. 47. The system of any one of claims 42-46, wherein the RGN of the fusion protein is an RGN nickase. 51. The system of claim 50, wherein the RGN nickase is any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398. 52. The system of any one of claims 42-51, wherein the fusion protein comprises one or more nuclear localization signals. 53. The system of any one of claims 42-52, wherein the fusion protein is codon optimized for expression in eukaryotic cells. 54. The system according to any one of claims 42 to 53, wherein the nucleotide sequence encoding the one or more guide RNAs and the nucleotide sequence encoding the fusion protein are located on one vector. A pharmaceutically acceptable carrier and the fusion protein of any one of claims 5 to 15, the nucleic acid molecule of any one of claims 16 to 30, the vector of any one of claims 31 to 34, claim 35 or a pharmaceutical composition comprising the cell of claim 36, or the system of any one of claims 42-54. A method of modifying a target DNA molecule comprising a target DNA sequence, the method comprising delivering a system according to any one of claims 42 to 54 to the target DNA molecule or a cell comprising the target DNA molecule. How to do. A method of modifying a target DNA molecule comprising a target sequence, comprising:
a) under conditions suitable for the formation of an RNA-guided nuclease polypeptide (RGN)-deaminase ribonucleotide complex
i) one or more guide RNAs capable of hybridizing to a target DNA sequence; and
ii) RGN and at least one deaminase, wherein the deaminase is at least 90 to any one of SEQ ID NOs: 407, 399, 405, 1-10, 400-404, 406, and 408-441 A fusion protein having an amino acid sequence with % sequence identity
Assembling the RGN-deaminase ribonucleotide complex in vitro by combining; and
b) contacting the target DNA molecule or a cell containing the target DNA molecule with an in vitro-assembled RGN-deaminase ribonucleotide complex.
contains;
wherein the one or more guide RNAs hybridize to the target DNA sequence, thereby directing the fusion protein to bind to the target DNA sequence, and modification of the target DNA molecule occurs.
method. 58. The method of claim 56 or 57, wherein the modified target DNA molecule comprises an A>N mutation of at least one nucleotide in the target DNA molecule, wherein N is C, G or T. 59. The method of claim 58, wherein the modified target DNA molecule comprises an A>G mutation of at least one nucleotide in the target DNA molecule. 60. The method of any one of claims 56-59, wherein the RGN of the fusion protein is a type II CRISPR-Cas polypeptide. 60. The method of any one of claims 56-59, wherein the RGN of the fusion protein is a type V CRISPR-Cas polypeptide. 60. The method of any one of claims 56-59, wherein the RGN of the fusion protein has an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 41, 60, 366, or 368. 60. The method of any one of claims 56-59, wherein the RGN of the fusion protein is an RGN nickase. 64. The method of claim 63, wherein the RGN nickase is any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398. 65. The method of any one of claims 56-64, wherein the fusion protein comprises one or more nuclear localization signals. 66. The method of any one of claims 56-65, wherein the fusion protein is codon optimized for expression in eukaryotic cells. 67. The method of any one of claims 56-66, wherein the target DNA sequence is a eukaryotic target DNA sequence. 68. The method of any one of claims 56-67, wherein the target DNA sequence is located adjacent to a protospacer adjacent motif (PAM). 69. The method of any one of claims 56-68, wherein the target DNA molecule is intracellular. 70. The method of claim 69, further comprising selecting cells comprising said modified DNA molecule. A cell comprising a target DNA sequence modified according to the method of claim 70 . A pharmaceutical composition comprising the cell of claim 71 and a pharmaceutically acceptable carrier. A method for producing genetically modified cells by correction of mutations causative for genetic hereditary disorders, comprising:
The method is
a) an RNA-guided nuclease polypeptide (RGN) and a deaminase, wherein the deaminase is SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 A fusion protein having an amino acid sequence having at least 90% sequence identity to any one of, or a polynucleotide encoding the fusion protein, wherein the polynucleotide encoding the fusion protein is capable of expressing the fusion protein in a cell. a polynucleotide operably linked to a promoter that allows; and
b) at least one guide RNA (gRNA) capable of hybridizing to a target DNA sequence, or a polynucleotide encoding said gRNA, wherein said polynucleotide encoding a gRNA is operable to a promoter enabling expression of the gRNA in a cell. Polynucleotides that are closely linked
Including introducing a;
Whereby the fusion protein and gRNA target the genomic location of the causative mutation and modify the genomic sequence to remove the causative mutation.
method. 74. The method of claim 73, wherein the RGN of the fusion protein is an RGN nickase. 75. The method of claim 74, wherein the RGN nickase is any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398. 76. The method of any one of claims 73-75, wherein the genomic modification comprises introducing an A>G mutation of at least one nucleotide in the target DNA sequence. 77. The method of any one of claims 73-76, wherein correcting the causal mutation comprises correcting a nonsense mutation. 74. The method of claim 73, wherein the genetic hereditary disease is a disease listed in Table 34. 74. The method of claim 73, wherein the hereditary inherited disease is cystic fibrosis. A method of treating a disease comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition of claim 55 or 72 . 81. The method of claim 80, wherein said disease is associated with a causal mutation, and said effective amount of said pharmaceutical composition corrects said causal mutation. The fusion protein of any one of claims 5 to 15, the nucleic acid molecule of any one of claims 16 to 30, the vector of any one of claims 31 to 34, an agent for treating a disease in a subject, Use of the cell of any one of claims 35, 36 or 71, or the system of any one of claims 42-54. 83. The use of claim 82, wherein said disease is associated with a causative mutation and said treatment comprises correcting said causative mutation. The fusion protein of any one of claims 5-15, the nucleic acid molecule of any one of claims 16-30, any one of claims 31-34, for the manufacture of a medicament useful for treating a disease. Use of the vector of claim 35 , the cell of any one of claims 36 and 71 , or the system of any one of claims 42 to 54 . 85. The use of claim 84, wherein said disease is associated with a causative mutation, and the effective amount of said medicament corrects said causative mutation. A nucleic acid molecule comprising a polynucleotide encoding an RNA-guided nuclease (RGN) polypeptide, wherein the polynucleotide has at least 95% sequence identity to SEQ ID NO: 41 or 60 but SEQ ID NO: 41 or a nucleotide sequence encoding an RGN polypeptide comprising an amino acid sequence lacking amino acid residues 590 to 597 of 60;
Wherein the RGN polypeptide is capable of binding to the target DNA sequence in an RNA-guide sequence specific manner when bound to a guide RNA (gRNA) capable of hybridizing to the target DNA sequence.
nucleic acid molecule. 87. The nucleic acid molecule of claim 86, wherein the polynucleotide encoding the RGN polypeptide is operably linked to a promoter heterologous to the polynucleotide. 88. The nucleic acid molecule of claim 86 or 87, wherein the RGN polypeptide is a nuclease malfunctioning or functions as a nickase. 89. The nucleic acid molecule of any one of claims 86-88, wherein the RGN polypeptide is operably fused to a base-edited polypeptide. A vector comprising the nucleic acid molecule of any one of claims 86-89. An isolated polypeptide comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 41 or 60 but lacking amino acid residues 590 to 597 of SEQ ID NO: 41 or 60, wherein the polypeptide is an RNA-guided nuclease. 92. The isolated polypeptide of claim 91, wherein said RGN polypeptide comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 366 or 368. 93. The isolated polypeptide of claim 91 or 92, wherein the RGN polypeptide is a nuclease malfunctioning or functions as a nickase. 94. The isolated polypeptide of any one of claims 91-93, wherein the RGN polypeptide is operably fused to a base-edited polypeptide. A cell comprising the nucleic acid molecule of any one of claims 86 - 89 , the vector of claim 90 , or the polypeptide of any one of claims 91 - 94 . An isolated polypeptide comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 407 and having deaminase activity. 97. The isolated polypeptide of claim 96 comprising the amino acid sequence set forth in SEQ ID NO:407. A nucleic acid molecule comprising a polynucleotide encoding a deaminase polypeptide, wherein the deaminase is:
a) have at least 80% sequence identity to SEQ ID NO: 451, or
b) encoding an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 407
which is encoded by a nucleotide sequence
nucleic acid molecule. 99. The nucleic acid molecule of claim 98, further comprising a heterologous promoter operably linked to said polynucleotide. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the polypeptide of any one of claims 96-97 or the nucleic acid molecule of any one of claims 98-99. A fusion protein comprising a DNA-binding polypeptide and a deaminase having at least 90% sequence identity to SEQ ID NO: 407. 102. The fusion protein of claim 101, wherein the DNA-binding polypeptide is an RNA-guided nuclease (RGN) polypeptide. 103. The fusion protein of claim 102, wherein the RGN polypeptide is a type II CRISPR-Cas polypeptide or a type V CRISPR-Cas polypeptide. 104. The method of any one of claims 101 to 103, wherein the RGN polypeptide is Cas9, CasX, CasY, Cpf1, C2c1, C2c2, C2c3, GeoCas9, CjCas9, Cas12a, Cas12b, Cas12g, Cas12h, Cas12i, Cas13b, Cas13c, Cas13d , Cas14, Csn2, xCas9, SpCas9-NG, LbCas12a, AsCas12a, Cas9-KKH, circular permutation Cas9, Argonauts (Ago), SmacCas9, Spy-macCas9 domain, or SEQ ID NO: 41, 60, 366, or 368 A fusion protein that is an RGN polypeptide having the amino acid sequence set forth in one. 105. The fusion protein of any one of claims 102-104, wherein the RGN polypeptide is a nickase. 106. The fusion protein of claim 105, wherein the nickase has an amino acid sequence with at least 95% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398. A nucleic acid molecule comprising a polynucleotide encoding a DNA-binding polypeptide and a fusion protein comprising a deaminase, wherein the deaminase comprises:
a) have at least 80% sequence identity to SEQ ID NO: 451, or
b) encoding an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 407
which is encoded by a nucleotide sequence
nucleic acid molecule. 108. The nucleic acid molecule of claim 107, wherein the DNA-binding polypeptide is an RGN polypeptide. 109. The nucleic acid molecule of claim 108, wherein the RGN is a Type II CRISPR-Cas polypeptide or a Type V CRISPR-Cas polypeptide. The method of any one of claims 107 to 109, wherein the RGN polypeptide is Cas9, CasX, CasY, Cpf1, C2c1, C2c2, C2c3, GeoCas9, CjCas9, Cas12a, Cas12b, Cas12g, Cas12h, Cas12i, Cas13b, Cas13c, Cas13d , Cas14, Csn2, xCas9, SpCas9-NG, LbCas12a, AsCas12a, Cas9-KKH, circular permutation Cas9, Argonauts (Ago), SmacCas9, Spy-macCas9 domain, or SEQ ID NO: 41, 60, 366, or 368 A nucleic acid molecule that is an RGN polypeptide having the amino acid sequence set forth in one. 111. The nucleic acid molecule of any one of claims 108-110, wherein the RGN polypeptide is a nickase. 112. The nucleic acid molecule of claim 111, wherein the nickase has an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398. A vector comprising the nucleic acid molecule of any one of claims 107-112. 114. The vector of claim 113, further comprising at least one nucleotide sequence encoding a guide RNA (gRNA) capable of hybridizing to the target sequence. A ribonucleoprotein (RNP) complex comprising the fusion protein of any one of claims 101 - 106 and a guide RNA linked to the DNA-binding polypeptide of the fusion protein. A cell comprising the fusion protein of any one of claims 101 to 106, the nucleic acid molecule of any one of claims 107 to 112, the vector of claim 113 or 114, or the RNP complex of claim 115. A system for modifying a target DNA molecule comprising a target DNA sequence, comprising:
The system
a) a fusion protein comprising an RNA-guided nuclease (RGN) polypeptide and a deaminase, wherein the deaminase has an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 407, or a nucleotide sequence encoding the fusion protein; and
b) one or more guide RNAs capable of hybridizing to the target DNA sequence, or one or more nucleotide sequences encoding one or more guide RNAs (gRNAs)
contains;
Wherein the one or more guide RNAs are capable of forming a complex with the fusion protein to direct the fusion protein to bind to the target DNA sequence and modify the target DNA molecule.
system. 118. The system of claim 117, wherein at least one of the nucleotide sequence encoding the one or more guide RNAs and the nucleotide sequence encoding the fusion protein is operably linked to a promoter heterologous to the nucleotide sequence. 119. The system of claim 117 or 118, wherein the target DNA sequence is located adjacent to a protospacer adjacent motif (PAM) recognized by the RGN polypeptide. 120. The method of any one of claims 117-119, wherein the target DNA sequences are SEQ ID NOs: 62-97, 116-139, 152-185, 203-234, 251-286, 305-344, 562 and 563 A system comprising a nucleic acid sequence selected from the group consisting of: 121. The method of any one of claims 117-120, wherein the gRNA sequence is from the group consisting of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564 A system comprising selected nucleic acid sequences. 122. The system of any one of claims 117-121, wherein the RGN polypeptide of the fusion protein is a Type II CRISPR-Cas polypeptide or a Type V CRISPR-Cas polypeptide. The method of any one of claims 117 to 122, wherein the RGN polypeptide is Cas9, CasX, CasY, Cpf1, C2c1, C2c2, C2c3, GeoCas9, CjCas9, Cas12a, Cas12b, Cas12g, Cas12h, Cas12i, Cas13b, Cas13c, Cas13d , Cas14, Csn2, xCas9, SpCas9-NG, LbCas12a, AsCas12a, Cas9-KKH, circular permutation Cas9, Argonaut (Ago), SmacCas9, Spy-macCas9 domain, or any one of SEQ ID NOs: 41, 60, 366 or 368 A system that is an RGN having the amino acid sequence set forth in. 124. The system of claim 123, wherein the RGN polypeptide is a nickcase. 125. The system of claim 124, wherein the nickase has an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398. A pharmaceutically acceptable carrier and the fusion protein of any one of claims 101 to 106, the nucleic acid molecule of any one of claims 107 to 112, the vector of any one of claims 113 to 114, the vector of any one of claims 115 A pharmaceutical composition comprising the RNP complex, the cell of claim 116 , or the system of any one of claims 117 - 125 . A method of modifying a target DNA molecule comprising a target sequence, comprising:
a) under conditions suitable for the formation of an RNA-guided nuclease polypeptide (RGN)-deaminase ribonucleotide complex
i) one or more guide RNAs capable of hybridizing to a target DNA sequence; and
ii) a fusion protein comprising RGN and at least one deaminase, wherein the deaminase has an amino acid sequence having at least 90% sequence identity to SEQ ID NO:407.
assembling an RGN-deaminase ribonucleotide complex by combining; and
b) contacting the target DNA molecule or a cell containing the target DNA molecule with the assembled RGN-deaminase ribonucleotide complex
contains;
wherein the one or more guide RNAs hybridize to the target DNA sequence, thereby directing the fusion protein to bind to the target DNA sequence, and modification of the target DNA molecule occurs.
method. 128. The method of claim 127, wherein the target DNA sequence is a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 62-97, 116-139, 152-185, 203-234, 251-286, 305-344, 562 and 563, or A method comprising its complement. 129. The method of any one of claims 127-128, wherein the gRNA sequence is from the group consisting of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564 A method comprising a selected nucleic acid sequence. 130. The method of any one of claims 127-129, performed in vitro, in vivo or ex vivo. A method of treating a subject having or at risk of developing a disease, disorder or condition comprising:
The above method
The fusion protein of any one of claims 101 to 106, the nucleic acid molecule of any one of claims 107 to 112, the vector of any one of claims 113 to 114, the RNP complex of claim 115, Administering the cell of claim 116, the system of any one of claims 117-125, or the pharmaceutical composition of claim 126.
which includes
method. 132. The method of claim 131, wherein any one of the gRNAs comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564 A method further comprising administering. An isolated polypeptide comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 405 and having deaminase activity. 134. The isolated polypeptide of claim 133 comprising the amino acid sequence set forth in SEQ ID NO: 405. A nucleic acid molecule comprising a polynucleotide encoding a deaminase polypeptide, wherein the deaminase is:
a) has at least 80% sequence identity to SEQ ID NO: 449, or
b) encoding an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 405
which is encoded by a nucleotide sequence
nucleic acid molecule. 136. The nucleic acid molecule of claim 135, further comprising a heterologous promoter operably linked to said polynucleotide. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the polypeptide of any one of claims 133 - 134 , or the nucleic acid molecule of any one of claims 135 - 136 . A fusion protein comprising a DNA-binding polypeptide and a deaminase having at least 90% sequence identity to SEQ ID NO: 405. 139. The fusion protein of claim 138, wherein the DNA-binding polypeptide is an RNA-guided nuclease (RGN) polypeptide. 140. The fusion protein of claim 139, wherein the RGN polypeptide is a type II CRISPR-Cas polypeptide or a type V CRISPR-Cas polypeptide. The method of any one of claims 138 to 140, wherein the RGN polypeptide is Cas9, CasX, CasY, Cpf1, C2c1, C2c2, C2c3, GeoCas9, CjCas9, Cas12a, Cas12b, Cas12g, Cas12h, Cas12i, Cas13b, Cas13c, Cas13d , Cas14, Csn2, xCas9, SpCas9-NG, LbCas12a, AsCas12a, Cas9-KKH, circular permutation Cas9, Argonaut (Ago), SmacCas9, Spy-macCas9 domain, or any one of SEQ ID NOs: 41, 60, 366 or 368 A fusion protein that is an RGN polypeptide having the amino acid sequence set forth in. 142. The fusion protein of any one of claims 139-141, wherein the RGN polypeptide is a nickase. 143. The fusion protein of claim 142, wherein the nickase has an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398. A nucleic acid molecule comprising a polynucleotide encoding a DNA-binding polypeptide and a fusion protein comprising a deaminase, wherein the deaminase comprises:
a) has at least 80% sequence identity to SEQ ID NO: 449, or
b) encoding an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 405
which is encoded by a nucleotide sequence
nucleic acid molecule. 145. The nucleic acid molecule of claim 144, wherein the DNA-binding polypeptide is an RGN polypeptide. 146. The nucleic acid molecule of claim 145, wherein the RGN is a Type II CRISPR-Cas polypeptide or a Type V CRISPR-Cas polypeptide. The method of any one of claims 144 to 146, wherein the RGN polypeptide is Cas9, CasX, CasY, Cpf1, C2c1, C2c2, C2c3, GeoCas9, CjCas9, Cas12a, Cas12b, Cas12g, Cas12h, Cas12i, Cas13b, Cas13c, Cas13d , Cas14, Csn2, xCas9, SpCas9-NG, LbCas12a, AsCas12a, Cas9-KKH, circular permutation Cas9, Argonauts (Ago), SmacCas9, Spy-macCas9 domain, or SEQ ID NO: 41, 60, 366, or 368 A nucleic acid molecule that is an RGN polypeptide having the amino acid sequence set forth in one. 148. The nucleic acid molecule of any one of claims 145-147, wherein the RGN polypeptide is a nickase. 149. The nucleic acid molecule of claim 148, wherein the nickase has an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398. A vector comprising the nucleic acid molecule of any one of claims 144-149. 151. The vector of claim 150, further comprising at least one nucleotide sequence encoding a guide RNA (gRNA) capable of hybridizing to the target sequence. A ribonucleoprotein (RNP) complex comprising the fusion protein of any one of claims 138 - 141 and a guide RNA linked to the DNA-binding polypeptide of the fusion protein. The fusion protein of any one of claims 138 to 143, the nucleic acid molecule of any one of claims 144 to 149, the vector of any one of claims 150 to 151, or the RNP complex of claim 152 cell. A system for modifying a target DNA molecule comprising a target DNA sequence, comprising:
The system
a) a fusion protein comprising an RNA-guided nuclease (RGN) polypeptide and a deaminase, wherein the deaminase has an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 405, or a nucleotide sequence encoding the fusion protein; and
b) one or more guide RNAs capable of hybridizing to the target DNA sequence, or one or more nucleotide sequences encoding one or more guide RNAs (gRNAs)
contains;
Wherein the one or more guide RNAs are capable of forming a complex with the fusion protein to direct the fusion protein to bind to the target DNA sequence and modify the target DNA molecule.
system. 155. The system of claim 154, wherein at least one of the nucleotide sequence encoding the one or more guide RNAs and the nucleotide sequence encoding the fusion protein is operably linked to a promoter heterologous to the nucleotide sequence. 156. The system of claim 154 or 155, wherein the target DNA sequence is located adjacent to a protospacer adjacent motif (PAM) recognized by the RGN polypeptide. 157. The method of any one of claims 154-156, wherein the target DNA sequences are SEQ ID NOs: 62-97, 116-139, 152-185, 203-234, 251-286, 305-344, 562 and 563 A system comprising a nucleic acid sequence selected from the group consisting of: 158. The method of any one of claims 154-157, wherein the gRNA sequence is from the group consisting of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564 A system comprising selected nucleic acid sequences. 159. The system of any one of claims 154-158, wherein the RGN polypeptide of the fusion protein is a Type II CRISPR-Cas polypeptide or a Type V CRISPR-Cas polypeptide. The method of any one of claims 154 to 159, wherein the RGN polypeptide is Cas9, CasX, CasY, Cpf1, C2c1, C2c2, C2c3, GeoCas9, CjCas9, Cas12a, Cas12b, Cas12g, Cas12h, Cas12i, Cas13b, Cas13c, Cas13d , Cas14, Csn2, xCas9, SpCas9-NG, LbCas12a, AsCas12a, Cas9-KKH, circular permutation Cas9, Argonaut (Ago), SmacCas9, Spy-macCas9 domain, or any one of SEQ ID NOs: 41, 60, 366 or 368 A system that is an RGN having the amino acid sequence set forth in. 161. The system of claim 160, wherein the RGN polypeptide is a nickcase. 162. The system of claim 161, wherein the nickase has an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398. A pharmaceutically acceptable carrier and the fusion protein of any one of claims 138-143, the nucleic acid molecule of any one of claims 144-149, the vector of any one of claims 150-151, A pharmaceutical composition comprising the RNP complex, the cell of claim 153 , or the system of any one of claims 154 - 162 . A method of modifying a target DNA molecule comprising a target sequence, comprising:
a) under conditions suitable for the formation of an RNA-guided nuclease polypeptide (RGN)-deaminase ribonucleotide complex
i) one or more guide RNAs capable of hybridizing to a target DNA sequence; and
ii) a fusion protein comprising RGN and at least one deaminase, wherein the deaminase has an amino acid sequence having at least 90% sequence identity to SEQ ID NO:405.
assembling an RGN-deaminase ribonucleotide complex by combining; and
b) contacting the target DNA molecule or a cell containing the target DNA molecule with the assembled RGN-deaminase ribonucleotide complex
contains;
wherein the one or more guide RNAs hybridize to the target DNA sequence, thereby directing the fusion protein to bind to the target DNA sequence, and modification of the target DNA molecule occurs.
method. 165. The method of claim 164, wherein the target DNA sequence is a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 62-97, 116-139, 152-185, 203-234, 251-286, 305-344, 562 and 563, or A method comprising its complement. 166. The method of claim 164 or 165, wherein the gRNA sequence is a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564 How to include. 167. The method of any one of claims 164-166, performed in vitro, in vivo or ex vivo. A method of treating a subject having or at risk of developing a disease, disorder or condition comprising:
The above method
The fusion protein of any one of claims 138 to 143, the nucleic acid molecule of any one of claims 144 to 149, the vector of any one of claims 150 to 151, the RNP complex of claim 152, Administering the cell of claim 153, the system of any one of claims 154-162, or the pharmaceutical composition of claim 163.
which includes
method. 169. The method of claim 168, wherein any one of the gRNAs comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564 A method further comprising administering. An isolated polypeptide comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 399 and having deaminase activity. 171. The isolated polypeptide of claim 170 comprising the amino acid sequence set forth in SEQ ID NO: 399. A nucleic acid molecule comprising a polynucleotide encoding a deaminase polypeptide, wherein the deaminase is:
a) have at least 80% sequence identity to SEQ ID NO: 443, or
b) encoding an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 399
which is encoded by a nucleotide sequence
nucleic acid molecule. 173. The nucleic acid molecule of claim 172, further comprising a heterologous promoter operably linked to said polynucleotide. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the polypeptide of any one of claims 170 - 171 or the nucleic acid molecule of any one of claims 172 - 173 . A fusion protein comprising a DNA-binding polypeptide and a deaminase having at least 90% sequence identity to SEQ ID NO: 399. 176. The fusion protein of claim 175, wherein the DNA-binding polypeptide is an RNA-guided nuclease (RGN) polypeptide. 177. The fusion protein of claim 176, wherein the RGN polypeptide is a type II CRISPR-Cas polypeptide or a type V CRISPR-Cas polypeptide. The method of any one of claims 175 to 177, wherein the RGN polypeptide is Cas9, CasX, CasY, Cpf1, C2c1, C2c2, C2c3, GeoCas9, CjCas9, Cas12a, Cas12b, Cas12g, Cas12h, Cas12i, Cas13b, Cas13c, Cas13d , Cas14, Csn2, xCas9, SpCas9-NG, LbCas12a, AsCas12a, Cas9-KKH, circular permutation Cas9, Argonaut (Ago), SmacCas9, Spy-macCas9 domain, or any one of SEQ ID NOs: 41, 60, 366 or 368 A fusion protein that is an RGN polypeptide having the amino acid sequence set forth in. 179. The fusion protein of any one of claims 176-178, wherein the RGN polypeptide is a nickase. 180. The fusion protein of claim 179, wherein the nickase has an amino acid sequence with at least 95% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398. A nucleic acid molecule comprising a polynucleotide encoding a DNA-binding polypeptide and a fusion protein comprising a deaminase, wherein the deaminase comprises:
a) have at least 80% sequence identity to SEQ ID NO: 443, or
b) encoding an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 399
which is encoded by a nucleotide sequence
nucleic acid molecule. 182. The nucleic acid molecule of claim 181, wherein the DNA-binding polypeptide is an RGN polypeptide. 183. The nucleic acid molecule of claim 182, wherein the RGN is a Type II CRISPR-Cas polypeptide or a Type V CRISPR-Cas polypeptide. The method of any one of claims 181 to 183, wherein the RGN polypeptide is Cas9, CasX, CasY, Cpf1, C2c1, C2c2, C2c3, GeoCas9, CjCas9, Cas12a, Cas12b, Cas12g, Cas12h, Cas12i, Cas13b, Cas13c, Cas13d , Cas14, Csn2, xCas9, SpCas9-NG, LbCas12a, AsCas12a, Cas9-KKH, circular permutation Cas9, Argonauts (Ago), SmacCas9, Spy-macCas9 domain, or SEQ ID NO: 41, 60, 366, or 368 A nucleic acid molecule that is an RGN polypeptide having the amino acid sequence set forth in one. 185. The nucleic acid molecule of any one of claims 182-184, wherein the RGN polypeptide is a nickase. 186. The nucleic acid molecule of claim 185, wherein the nickase has an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398. A vector comprising the nucleic acid molecule of any one of claims 181 - 186 . 188. The vector of claim 187, further comprising at least one nucleotide sequence encoding a guide RNA (gRNA) capable of hybridizing to the target sequence. A ribonucleoprotein (RNP) complex comprising the fusion protein of any one of claims 175 - 180 and a guide RNA linked to the DNA-binding polypeptide of the fusion protein. The fusion protein of any one of claims 175 to 180, the nucleic acid molecule of any one of claims 181 to 186, the vector of any one of claims 187 to 188, or the RNP complex of claim 189 cell. A system for modifying a target DNA molecule comprising a target DNA sequence, comprising:
The system
a) a fusion protein comprising an RNA-guided nuclease (RGN) polypeptide and a deaminase, wherein the deaminase has an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 399, or a nucleotide sequence encoding the fusion protein; and
b) one or more guide RNAs capable of hybridizing to the target DNA sequence, or one or more nucleotide sequences encoding one or more guide RNAs (gRNAs)
contains;
Wherein the one or more guide RNAs are capable of forming a complex with the fusion protein to direct the fusion protein to bind to the target DNA sequence and modify the target DNA molecule.
system. 192. The system of claim 191, wherein at least one of the nucleotide sequence encoding the one or more guide RNAs and the nucleotide sequence encoding the fusion protein is operably linked to a promoter heterologous to the nucleotide sequence. 193. The system of claim 191 or 192, wherein the target DNA sequence is located adjacent to a protospacer adjacent motif (PAM) recognized by the RGN polypeptide. 194. The method of any one of claims 191-193, wherein the target DNA sequences are SEQ ID NOs: 62-97, 116-139, 152-185, 203-234, 251-286, 305-344, 562 and 563 A system comprising a nucleic acid sequence selected from the group consisting of: 195. The method of any one of claims 191-194, wherein the gRNA sequence is from the group consisting of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564 A system comprising selected nucleic acid sequences. 196. The system of any one of claims 191-195, wherein the RGN polypeptide of the fusion protein is a Type II CRISPR-Cas polypeptide or a Type V CRISPR-Cas polypeptide. The method of any one of claims 191 to 196, wherein the RGN polypeptide is Cas9, CasX, CasY, Cpf1, C2c1, C2c2, C2c3, GeoCas9, CjCas9, Cas12a, Cas12b, Cas12g, Cas12h, Cas12i, Cas13b, Cas13c, Cas13d , Cas14, Csn2, xCas9, SpCas9-NG, LbCas12a, AsCas12a, Cas9-KKH, circular permutation Cas9, Argonaut (Ago), SmacCas9, Spy-macCas9 domain, or any one of SEQ ID NOs: 41, 60, 366 or 368 A system that is an RGN having the amino acid sequence set forth in. 198. The system of claim 197, wherein the RGN polypeptide is a nickase. 199. The system of claim 198, wherein the nickase has an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398. A pharmaceutically acceptable carrier and the fusion protein of any one of claims 175 - 180 , the nucleic acid molecule of any one of claims 181 - 186 , the vector of any one of claims 187 - 188 , the vector of any one of claims 189 A pharmaceutical composition comprising the RNP complex, the cell of claim 190, or the system of any one of claims 191-199. A method of modifying a target DNA molecule comprising a target sequence, comprising:
a) under conditions suitable for the formation of an RNA-guided nuclease polypeptide (RGN)-deaminase ribonucleotide complex
i) one or more guide RNAs capable of hybridizing to a target DNA sequence; and
ii) a fusion protein comprising RGN and at least one deaminase, wherein the deaminase has an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 399
assembling an RGN-deaminase ribonucleotide complex by combining; and
b) contacting the target DNA molecule or a cell containing the target DNA molecule with the assembled RGN-deaminase ribonucleotide complex
contains;
wherein the one or more guide RNAs hybridize to the target DNA sequence, thereby directing the fusion protein to bind to the target DNA sequence, and modification of the target DNA molecule occurs.
method. 201. The method of claim 201, wherein the target DNA sequence is a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 62-97, 116-139, 152-185, 203-234, 251-286, 305-344, 562 and 563, or A method comprising its complement. 203. The method of any one of claims 201-202, wherein the gRNA sequence is from the group consisting of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564 A method comprising a selected nucleic acid sequence. 204. The method of any one of claims 201-203, performed in vitro, in vivo or ex vivo. A method of treating a subject having or at risk of developing a disease, disorder or condition comprising:
The above method
The fusion protein of any one of claims 175 to 180, the nucleic acid molecule of any one of claims 181 to 186, the vector of any one of claims 187 to 188, the RNP complex of claim 189, Administering the cell of claim 190, the system of any one of claims 191-199, or the pharmaceutical composition of claim 200.
which includes
method. 206. The method of claim 205, wherein any one of the gRNAs comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564 A method further comprising administering. A method of treating or reducing at least one symptom of cystic fibrosis, comprising:
The method can be used to administer an effective amount to a subject in need thereof.
a) an RNA-guided nuclease polypeptide (RGN) and a deaminase, wherein the deaminase is SEQ ID NOs: 407, 405, 399, 1-10, 400-404, 406, and 408-441 A fusion protein having an amino acid sequence having at least 90% sequence identity to any one of, or a polynucleotide encoding the fusion protein, wherein the polynucleotide encoding the fusion protein is capable of expressing the fusion protein in a cell. a polynucleotide operably linked to a promoter that allows; and
b) at least one guide RNA (gRNA) capable of hybridizing to a target DNA sequence, or a polynucleotide encoding said gRNA, wherein said polynucleotide encoding a gRNA is operable to a promoter enabling expression of the gRNA in a cell. Polynucleotides that are closely linked
Including introducing a;
Whereby the fusion protein and gRNA target the genomic location of the causative mutation and modify the genomic sequence to remove the causative mutation.
method. 208. The method of claim 207, wherein the gRNA targets any one of SEQ ID NOs: 62-97, 116-139, 152-185, 203-234, 251-286, 305-344, 562 and 563, or the complement thereof. A method comprising a spacer sequence. 209. The method of claim 207 or 208, wherein the gRNA comprises any one of SEQ ID NOs: 98-115, 140-151, 186-202, 235-250, 287-304, 345-364 and 564. . 210. The method of any one of claims 207-209, wherein said RGN has an amino acid sequence with at least 90% sequence identity to any one of SEQ ID NOs: 41, 60, 366 and 368. 210. The method of any one of claims 207-209, wherein the RGN has an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 42, 52-59, 61, 397 and 398. method.